Kinetics of cytokine and chemokine responses in patients with primary human herpesvirus 6 infection

BackgroundCytokines and chemokines induced by human herpesvirus 6 (HHV-6) infection may play an important role in the observed HHV-6-associated clinical complications. However, basic data for cytokine and chemokine synthesis in primary HHV-6 infected patient without complication is lacking.ObjectiveAim of this study was to elucidate basic kinetic data for expressions of cytokines and chemokines in patients with primary HHV-6 infection without complication.Study designTwenty-six patients suffering from fever were enrolled in this study. Fourteen biomarkers were measured in 74 serially collected sera samples from 26 patients. Additionally, serum samples obtained from 14 healthy children were used for control.ResultsTwenty of the 26 patients were diagnosed with primary HHV-6 infection based on viral isolation and serological analysis. The mean age (P = 0.1289) and proportion of males to females (P = 0.9999) between the patients with and without primary HHV-6 infection were not statistically different. At the acute phase of the disease, three cytokines (IFN-γ; P = 0.0046, IL-2; P = 0.0366, and IL-4; P = 0.0255) and one chemokine (MCP-1; P = 0.0019) were significantly higher in patients with primary HHV-6 infection compared to those without infection. Interleukin-5 levels during the convalescent period were significantly higher in patients with HHV-6 infection (P = 0.0205). By 1 month post-infection, cytokine and chemokine expression had returned to almost basal levels.ConclusionAs suggested by the previous in vitro studies, present in vivo analysis also suggests that HHV-6 has potency for induction of cytokines and chemokines.     

Echinococcus multilocularis metacestodes modulate cellular cytokine and chemokine release by peripheral blood mononuclear cells in alveolar echinococcosis patients

Infection with the cestode Echinococcus multilocularis causes human alveolar echinococcosis (AE), a life-threatening disease affecting primarily the liver. Despite the severity of AE, clinical symptoms often develop only many years after infection, which suggests that E. multilocularis has developed mechanisms which depress anti-parasite immune response, thus favouring immune evasion. In this study we examined the production of cytokines, chemokines and the expression of CD molecules on peripheral blood mononuclear cells (PBMC) from AE patients and healthy controls in response to E. multilocularis metacestode culture supernatant, viable E. multilocularis vesicles and E. multilocularis vesicle fluid antigen in vitro. After 48 h of co-culture, E. multilocularis metacestode culture supernatant and E. multilocularis vesicles depressed the release of the proinflammatory cytokine interleukin (IL)-12 by PBMC. This effect was dose-dependent and a suppression of tumour necrosis factor (TNF)-alpha and IL-12 was observed even when PBMC were activated with lipopolysaccharide (LPS). Comparing proinflammatory cytokine release by AE patients and controls showed that the release of IL-12 and TNF-alpha was reduced in AE patients, which was accompanied by an increased number of CD4+ CD25+ cells and a reduced release of the Th2 type chemokine CCL17 (thymus and activation regulated chemokine, TARC), suggesting an anti-inflammatory response to E. multilocularis metacestode in AE patients. Instead the production of interferon (IFN)-gamma and the expression of CD28 on CD4+ T cells were increased in PBMC from AE patients when compared to controls. This was accompanied by a higher release of the Th2-type chemokine CCL22 (macrophage derived chemokine, MDC) supporting that E. multilocularis also generates proinflammatory immune responses. These results indicate that E. multilocularis antigens modulated both regulatory and inflammatory Th1 and Th2 cytokines and chemokines. Such a mixed profile might be required for limiting parasite growth but also for reducing periparasitic tissue and organ damage in the host.     

Serum cytokine and chemokine profiles in patients with myasthenia gravis

Myasthenia gravis (MG) is an autoimmune‐mediated inflammatory disease of the neuromuscular junction. Previous studies of animal MG models have suggested important roles of cytokines in MG pathogenesis, but adequate studies on cytokines in human MG are lacking. Using a multiplex suspension array system, we measured the serum levels of 27 cytokines/chemokines in 47 anti‐acetylcholine receptor antibody‐positive patients with MG and 20 normal controls (NC) to investigate the contribution of cytokines/chemokines toward MG pathogenesis. Correlations between clinical parameters and cytokine/chemokine levels in patients with MG were also examined. The serum levels of interleukin (IL)‐15 (mean ± standard deviation: 6·85 ± 6·97 pg/ml) and vascular endothelial growth factor (VEGF) (96·21 ± 71·60 pg/ml) significantly increased, whereas IL‐4 levels (3·57 ± 0·86 pg/ml) decreased in patients with MG compared with NC (IL‐15: 4·42 ± 1·55 pg/ml; VEGF: 63·51 ± 32·95 pg/ml; IL‐4: 4·15 ± 0·81 pg/ml, P < 0·05). In addition, eight cytokines (IL‐4, IL‐8, IL‐15, eotaxin, macrophage inflammatory protein‐1α, macrophage inflammatory protein‐1β, VEGF and IL‐1b) were significantly changed among MG patients with thymoma, MG patients without thymoma and NC (P < 0·05). Some cytokines, such as IL‐4, IL‐15, and VEGF, may play roles in the pathogenesis of MG.     

Inflammatory and regulatory CCL and CXCL chemokine and cytokine cellular responses in patients with patent Mansonella perstans filariasis

Mansonella perstans (Mp) filariasis is present in large populations in sub-Saharan Africa, and to what extent patent Mp infection modulates the expression of immunity in patients, notably their cellular cytokine and chemokine response profile, remains not well known. We studied the spontaneous and inducible cellular production of chemokines (C-X-C motif) ligand 9 (CXCL9) [monokine induced by interferon (IFN)-γ (MIG)], CXCL-10 [inducible protein (IP)-10], chemokine (C-C motif) ligand 24 (CCL24) (eotaxin-2), CCL22 [macrophage-derived chemokine (MDC)], CCL13 [monocyte chemotactic protein-4 (MCP-4)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], CCL17 [thymus- and activation-regulated chemokine (TARC)] and interleukin (IL)-27 in mansonelliasis patients (Mp-PAT) and mansonelliasis-free controls (CTRL). Freshly isolated peripheral mononuclear blood cells (PBMC) were stimulated with helminth, protozoan and bacterial antigens and mitogen [phytohaemagglutinin (PHA)]. PBMC from Mp-PAT produced spontaneously (without antigen stimulation) significantly higher levels of eotaxin-2, IL-27, IL-8, MCP-4 and MDC than cells from CTRL, while IFN-γ-IP-10 was lower in Mp-PAT. Helminth antigens activated IL-27 and MCP-4 only in CTRL, while Ascaris antigen, Onchocerca antigen, Schistosoma antigen, Entamoeba antigen, Streptococcus antigen, Mycobacteria antigen and PHA stimulated MIG release in CTRL and Mp-PAT. Notably, Entamoeba antigen and PHA strongly depressed (P < 0·0001) eotaxin-2 (CCL24) production in both study groups. Multiple regression analyses disclosed in Mp-PAT and CTRL dissimilar cellular chemokine and cytokine production levels being higher in Mp-PAT for CCL24, IL-27, IL-8, MCP-4, MDC and PARC (for all P < 0·0001), at baseline (P < 0·0001), in response to Entamoeba histolytica strain HM1 antigen (EhAg) (P < 0·0001), Onchocerca volvulus adult worm-derived antigen (OvAg) (P = 0·005), PHA (P < 0·0001) and purified protein derivative (PPD) (P < 0·0001) stimulation. In Mp-PAT with hookworm co-infection, the cellular chemokine production of CXCL10 (IP-10) was diminished. In summary, the chemokine and cytokine responses in Mp-PAT were in general not depressed, PBMC from Mp-PAT produced spontaneously and selectively inducible inflammatory and regulatory chemokines and cytokines at higher levels than CTRL and such diverse and distinctive reactivity supports that patent M. perstans infection will not polarize innate and adaptive cellular immune responsiveness in patients.     

Tissue cytokine and chemokine expression in inflammatory bowel disease

OBJECTIVE AND DESIGN: This study aimed to determine if mucosal expression of the chemokines IL-8, RANTES and MCP-1 and the pro-inflammatory cytokines TNFalpha and IL-6 are elevated in patients with inflammatory bowel disease. MATERIALS AND SUBJECTS: Intestinal mucosa samples were obtained at the time of surgical resection, n = 16 from each of the following groups: normal/control, CD and UC. METHODS: An homogenate was prepared of each tissue sample and cytokines measured by ELISA. RESULTS: IL-8 was significantly increased in both disease groups compared to controls Similarly, RANTES levels were also significantly increased. MCP-1 levels were increased in both disease groups, this increase was statistically significant in the UC group only. TNFalpha and IL-6 were significantly increased in the CD group only. CONCLUSIONS: Chemokines, together with key cytokines that promote their release are elevated in mucosal tissues from patients with IBD. It is likely that these chemokines play an important role in the perpetuation of tissue destructive inflammatory processes.     

Complexity and function of cytokine responses in experimental infection by Echinococcus granulosus

Cytokines are important in the regulation of the immune system and are secreted by a variety of cells in response to self and non-self stimuli. Communication within cells, in the same or distant anatomical sites, occurs via cytokines which determine the quality and intensity of inflammatory and adaptive immune responses. Infection by helminths is characterized by a dominant secretion of type-2 cytokines; IL-4, IL-5, IL-10 (among others), which down-regulates the induction and functions of type-1 cytokines. The molecular mechanisms involved in the polarization of type-2 responses and their biological significance in helminthic infections are unknown, and probably depends on each host-parasite system. Understanding these issues may contribute to immune therapy against parasitic infections. Here we summarize our data obtained in Echinococcus granulosus experimental infection regarding type-2 cytokine induction and its putative role in the host-parasite interaction. Results suggest that induction of cytokine responses at different stages of infection is complex and depends on several parameters. In addition, they support the hypothesis that early IL-10, secreted by B cells in response to non-proteic antigens, may favour parasite survival and the establishment of a polarized type-2 cytokine response.     

Resistance/susceptibility to Echinococcus multilocularis infection and cytokine profile in humans. I. Comparison of patients with progressive and abortive lesions

To clarify the role of Th1- and Th2-type cytokines in the various outcomes of human alveolar echinococcosis (AE), the cytokine immune response of self-cured patients was studied and compared with those of progressive AE patients and healthy subjects. Self-cured patients were divided into two groups according to the following clinical features: subjects who had positive Echinococcus multilocularis serologies and hepatic calcifications typical of AE were classified as 'abortive AE' patients, and those who had positive E. multilocularis serologies but no hepatic lesions or calcifications detectable by ultrasonography were classified as 'positive serology' subjects. Secretions of IL-5, IL-10 and interferon-gamma, and expression of IL-5 mRNA were evaluated in peripheral blood mononuclear cells (PBMC) stimulated in vitro with the mitogen phytohaemagglutinin-C or specific E. multilocularis antigenic preparations. The cytokine profile of abortive AE patients was the opposite of that observed in progressive AE patients. An intermediate profile was observed in positive serology subjects. PBMC from abortive AE patients, whether non-stimulated or stimulated with PHA and antigenic preparations, secreted significantly lower levels of IL-10 than those isolated from progressive AE patients. Our observations seem to confirm the regulatory role of IL-10 in the immunopathology of human AE.     

Inflammatory cytokine levels in patients with periodontitis and/or coronary heart disease

The purpose of this study was to investigate systemic and local levels of four classic inflammatory cytokines (IL-1β, MCP-1, VEGF, PDGF) in patients with periodontitis and coronary heart disease (CHD). 109 volunteers were enrolled and the condition of their periodontal tissue and coronary artery were assessed. The patients were then divided into four distinct groups: periodontitis only, CHD only, periodontitis with CHD, and healthy controls. Gingival crevicular fluid (GCF) and venous blood were collected. The concentrations of cytokines were detected meanwhile by specific ELISA. The IL-1β and MCP-1 concentrations in the serum and GCF of the three disease groups were significantly higher than those in the control group (P ≤ 0.05). Serum VEGF concentrations of the patients with existing disease was lower than that of the controls. VEGF levels in the GCF of all disease groups were significantly higher than that of the control group (P ≤ 0.05).     

Rotavirus-specific subclass antibody and cytokine responses in Bangladeshi children with rotavirus diarrhoea

Rotavirus-specific subclass antibody responses and cytokines, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-8 (IL-8), and IL-10, were measured in children 7-24 months of age with rotavirus diarrhoea (n = 29); the responses were compared with children with watery diarrhoea from whom no enteric pathogens were isolated (controls; n = 11). All children had diarrhoea for < 5 days and were enrolled from the Dhaka Hospital of the Centre for Health and Population Research. Samples of blood and stools were collected on the day of enrollment and 18-21 days after the onset of diarrhoea. Children showing a > or = 4-fold rise in antibody titre between the acute and convalescent stages were considered to have a response. The numbers of children with rotavirus-specific IgA and IgA1 responses in stool were similar in the two groups of children. In the plasma, more children with rotavirus diarrhoea had rotavirus-specific IgA, IgA1, IgG, IgG1, and IgG3 responses than did control children (P = 0.049, 0.007, 0.001, 0.002, and 0.012, respectively). IgA2 was not detectable. Among cytokines measured in supernatants from peripheral blood mononuclear cells (PBMCs) cultured for 6 and 24 hr, IFN-gamma was the only cytokine that was higher in children with rotavirus diarrhoea compared with controls (P = 0.013). Severity of illness did not correlate with nutritional status or antibody titres, but severity did correlate with TNF-alpha during the acute stage of illness. IFN-gamma correlated positively with IgG1 titres. These findings suggest a role for IFN-gamma in the pathogenesis of rotavirus infection, but this needs confirmation by other studies. The immune responses described are relevant to future vaccine trials, as immune responses in vaccinees should mimic those in natural infection.     

Antinuclear antibody and lymphocyte responses to nuclear antigens in patients with lung disease

The in vitro peripheral leucocyte migration test was used to study cell-mediated hypersensitivity to whole rat liver nuclei, calf thymus deoxyribonucleoprotein and highly polymerized calf thymus deoxyribonucleic acid (DNA) in patients with circulating antinuclear antibody (ANA) suffering from different pulmonary diseases.

The group with pleuropulmonary systemic lupus erythematosus (SLE) showed significant inhibition of leucocyte migration to whole nuclei (P<0·001), DNA (P<0·025) and to nucleoprotein (P<0·05). In contrast, the groups of ANA-positive patients with cryptogenic fibrosing alveolitis (CFA) and asbestosis showed inhibition only to DNA (P<0·025). Individual patients with CFA and asbestosis showed evidence of lymphocyte sensitization to whole nuclei as well as to DNA. Involvement of delayed hypersensitivity to nuclear antigens in tissue damage is therefore possible in some, but not all patients with these diseases.

There was no evidence of lymphocyte sensitization in any ANA-positive patients with intrinsic asthma, systemic sclerosis or Sjögren's syndrome.

Corticosteroid therapy substantially reduced inhibition of leucocyte migration to whole nuclei and DNA in patients with SLE and CFA.

From these studies it is concluded that lymphocyte sensitization is not constantly related to circulating ANA in patients with different types of pulmonary disease, and that nuclear antigens appear to stimulate variable immunological responses and it is suggested that this may depend upon the initiating circumstances and the host response.

     

Apoptotic cells inhibit LPS-induced cytokine and chemokine production and IFN responses in macrophages

Apoptosis is a critical process in tissue homeostasis and results in immediate removal of the dying cell by professional phagocytes such as macrophages and dendritic cells. Phagocytosis of apoptotic cells actively suppresses production of proinflammatory growth factors and cytokines. Impaired phagocytosis of apoptotic cells has been implicated in the pathogenesis of chronic inflammatory and autoimmune diseases. In this study we found that, in addition to suppressing lipopolysaccharide (LPS)-induced production of TNF-alpha and IL-6, phagocytosis of apoptotic cells by macrophages suppressed production of the chemokine CXCL10 that is activated by LPS-induced autocrine-acting type I IFNs. Inhibition of cytokine and chemokine production was not universally affected because LPS-induced production of IL-10 and IL-8 was not significantly affected. Apoptotic cells had minimal effects on LPS-induced activation of NF-kappaB and MAPKs, but induced expression of SOCS proteins and substantially suppressed induction of CXCL10 expression by IFN-alpha. In addition to suppressing LPS responses, apoptotic cells inhibited macrophage responses to another major macrophage activator IFN-gamma by attenuating IFN-gamma-induced STAT1 activation and downstream gene expression. These results identify suppressive effects of apoptotic cells on signal transduction, and extend our understanding of the anti-inflammatory effects of apoptotic cells to include suppression of Jak-STAT signaling.     

Interleukin 2 production in patients with Chagas' disease: correlation with anti-parasite antibody responses

Peripheral blood mononuclear cells (PBMC) isolated from chronic chagasic patients and control individuals in Recife, Brazil were examined for the ability to produce IL-2 in response to concanavalin A (Con A) stimulation. Overall, there was little difference in the range of the response (IL-2 production) between the chagasic and control groups. Within the chagasic group, however, there was a high negative correlation between IL-2 production and the level of anti-parasite antibody. This correlation is thought to be a reflection of the fact that individuals with more recent or more vigorous infections exhibit higher anti-parasite antibody responses but also display a greater degree of immunosuppression, as reflected in depressed IL-2 production.     

Onchocerca volvulus-specific antibody and cytokine responses in onchocerciasis patients after 16 years of repeated ivermectin therapy

The recommended control option against onchocerciasis is repeated ivermectin treatment, which will need to be implemented for decades, and it remains unknown how repeated ivermectin therapy might affect immunity against Onchocerca volvulus in the long term. O. volvulus-specific antibody reactivity and cellular cytokine production were investigated in onchocerciasis patients receiving ivermectin (150 microg/kg) annually for 16 years. In treated patients, the T helper type 2 (Th2) cytokine interleukin (IL)-5 and T regulatory IL-10 in response to O. volvulus antigen (OvAg) and bacteria-derived Streptolysin O (SL-O) diminished to levels found in infection-free endemic controls; also, cellular release of Th1-type interferon (IFN)-gamma at 16 years post initial ivermectin treatment (p.i.t.) approached control levels. In ivermectin-treated onchocerciasis patients, IL-5 production in responses to the mitogen phytohaemagglutinin (PHA) decreased, but IL-10 in response PHA increased, and neither attained the cytokine production levels of endemic controls. At 16 years p.i.t., O. volvulus-specific IgG1 and IgG4 subclass reactivity still persisted at higher levels in onchocerciasis patients than in O. volvulus exposed but microfilariae-free endemic controls. In addition, cytokine responses remained depressed in onchocerciasis patients infected concurrently with Mansonella perstans and Necator americanus or Entamoeba histolytica/dispar. Thus, long-term ivermectin therapy of onchocerciasis may not suffice to re-establish fully a balanced Th1 and Th2 immune responsiveness in O. volvulus microfilariae-negative individuals. Such deficient reconstitution of immune competence may be due to an as yet continuing and uncontrolled reinfection with O. volvulus, but parasite co-infections can also bias and may prevent the development of such immunity.     

Distinctive abnormal responses to tilting test in chronic chagas' disease

Summary The purpose of this study was to investigate the sympathetic nervous system function in 34 patients with chronic Chagas' disease. The tilting test was selected as an appropriate means to assess the adrenergic system function.Our results demonstrate that (a) all chagasics respond with a significantly smaller rise in diastolic blood pressure (0–3.8 mmHg) than normal subjects (9–12 mmHg), when submitted to the tilting test and (b) chagasic patients with heart failure have a significantly lower heart rate than normal subjects and non-chagasic heart failure patients (P<0.05 and 0.001, respectively).With these results we may speculate that the damage in chronic Chagas' disease should be located in the sympathetic pathway. Therefore, the faulty orthostatic mechanism would be the consequence of a diminished adrenergic activity, with a defective arteriolar vasoconstriction and a decreased basal heart rate.At the same time we note that our results differ from the results of similar tests performed on the same kind of chagasic patients in Brazil, where a predominantly decreased parasymphathetic activity has been demonstrated.This work was supported in part by Tubos Transelectric and Renault Argentina     

Expression of cytokine and chemokine genes in Epstein-Barr virus-associated nasopharyngeal carcinoma: comparison with Hodgkin's disease

Nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD) are characterized by their association with Epstein-Barr virus (EBV) and the presence of an intense lymphoid stroma, consisting of T lymphocytes and other reactive cells. In both entities, the tumour cells express viral proteins known to provide target epitopes for cytotoxic T-cells (CTLs), yet in vivo, the tumour cells appear to escape CTL recognition. A comparative in situ hybridization study of cytokine and chemokine gene expression in NPC and HD has been undertaken, focusing on cytokines which are known to be inducible by EBV in vitro. Hodgkin and Reed-Sternberg (HRS) cells expressed interleukin (IL)-6, IL-8, and IL-10, and the thymus and activation regulated chemokine (TARC) in 15/22, 0/22, 5/22, and 16/21 cases, respectively. In NPC, the epithelial tumour cells showed expression of IL-6 in 3/43 cases and of IL-8 in 2/40 cases. There was no detectable expression of IL-10 and TARC in these cases. These data confirm that HRS cells frequently express cytokine and chemokine genes and suggest that this may enable HRS cells to modulate the immune response in their microenvironment and to escape CTL detection. In contrast, NPC tumour cells show only rare expression of IL-6 and IL-8 and no detectable expression of IL-10 and TARC. Thus, the results suggest that the mechanisms employed by the EBV-positive tumour cells to escape immune recognition and destruction differ between HD and NPC.     

Assessment of in vitro cytokine response in hemophilia A patients with or without factor VIII inhibitory antibody.

Factor VIII (FVIII) inhibitor antibodies are produced in a proportion of hemophilia A patients. Development of anti-FVIII inhibitor antibodies is a T cell-dependent response, mediated by FVIII specific CD4(+) T cells. This study was performed to investigate the contribution of T helper (Th) cell-mediated cytokine response in inhibitor production. Peripheral blood mononuclear cells (PBMCs) were obtained from hemophilia A patients with (n = 14) or without inhibitor (n = 14) and from normal individuals (n = 14). Following stimulation of PBMCs with rFVIII and phytohemagglutinin (PHA) mitogen, the secreted cytokines, interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and transforming growth factor-beta1 (TGF-beta1), in culture supernatant and the proliferative response were assessed using sandwich ELISA and (3)H-thymidine incorporation, respectively. No significant proliferative response to FVIII was observed, whereas PHA induced a strong response in all groups. No cytokine secretion was observed in response to FVIII stimulation. Although PHA induced IL-10, TGF-beta1 and IFN-gamma secretion in all groups, the level of IFN-gamma was significantly lower in hemophilia A patients than in normal individuals (p < 0.0001). The levels of TGF-beta1 and IL-10 were similarly higher in patients compared with normal subjects, but the difference was not statistically significant. Lack of FVIII-induced proliferative response and cytokine production together with reduced secretion of PHA-induced IFN-gamma in both groups of patients suggest involvement of nonspecific immunosuppression possibly due to hepatitis C virus (HCV) infection observed in the majority of patients.     

Enterovirus-specific serum IgA antibody responses in patients with acute infections, chronic cardiac disease, and recently diagnosed insulin-dependent diabetes mellitus

Employing an antibody class capture ELISA, we assessed the significance of enterovirus (EV)-specific serum IgA (EV-IgA) as a marker of EV infection. EV-IgA was detectable in 64% of sera from patients with acute illnesses which may be attributable to EV infection who also had EV-IgM, but also in 30% of sera from patients without evidence of EV infection. High EV-IgA levels were more closely associated with the presence of EV-IgM and were demonstrable in 39% of patients with acute infections who were EV-IgM positive, compared to 3% of those who were EV-IgM negative. Among patients with acute EV infection confirmed by virus isolation, EV-IgA was present in 67% and EV-IgM was present in 83%. As a marker of acute EV infection, EV-IgA is less sensitive and less specific than EV-IgM. EV-IgA responses in patients with chronic cardiac disease paralleled EV-IgM responses in some cases but there was no significant association between these two antibody responses in this group as a whole. High EV-IgA responses were present in 20% of EV-IgM positive and 21% of EV-IgM negative patients, and may persist as a result of an immunoregulatory defect leading to virus or antigen persistence at mucosal surfaces. High EV-IgA levels were also detectable in 33% of EV-IgM positive newly diagnosed insulin-dependent diabetics but in none who were EV-IgM negative, which suggests that most EV infections in these patient were acute rather than persistent.     

Cervical cytokine responses in women with primary or recurrent chlamydial infection.

Little is known about concurrent expression of cervical cytokines and their regulation by sex hormones during primary or recurrent chlamydial infections in humans. Cytokine (interleukin-1beta [IL-1beta], IL-6, IL-10, interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) concentrations in cervical washes and serum samples, along with levels of beta-estradiol and progesterone in women with primary or recurrent chlamydial infections and healthy controls, were measured by ELISA. Women with recurrent infections had significantly higher levels of IFN-gamma in cervical washes than did women with primary infections. Significant negative correlation was found between IL-1beta and progesterone levels during recurrent infections. Beta-estradiol levels in women with primary infections showed significant negative correlations with cervical concentrations of IL-10, IL-1beta, and IL-6. Our study suggests that Chlamydia trachomatis infection in the female genital tract may be regulated by both the synergistic actions of the cytokines and the sex hormones beta-estradiol and progesterone.     

HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease.

Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena.