Candida albicans enhances invasion of human gingival epithelial cells and gingival fibroblasts by Porphyromonas gingivalis

Although Candida albicans has been isolated from periodontal pockets, its relationship to periodontitis is unclear. In this study, we investigated the effect of C. albicans on the adhesion and invasion of Ca9-22, a human gingival epithelial cell line, and human gingival fibroblasts by Porphyromonas gingivalis. Heat-killed C. albicans and water-soluble mannoprotein-β-glucan complex from C. albicans (CAWS) did not enhance P. gingivalis adhesion or upregulate the expression of β1 integrin and ICAM-1, which are required for P. gingivalis invasion; both the epithelial cells and fibroblasts expressed dectin-1, which recognizes components of the C. albicans cell wall. However, pretreatment of Ca9-22 cells and human gingival fibroblasts with heat-killed C. albicans or CAWS significantly enhanced P. gingivalis invasion. These results suggest that C. albicans may exacerbate infectious disease by enhancing the invasion of host cells by anaerobic bacteria.     

Suppression of inflammatory gene expression in T cells by Porphyromonas gingivalis is mediated by targeting MAPK signaling

There is increasing awareness of the effects of Porphyromonas gingivalis on host immune responses. Degradation of cytokines and chemokines by cysteine proteinases has previously been reported. However, the precise mechanisms by which P. gingivalis is able to alter intracellular signaling, and thus proliferation and inflammation, have not been described. We have previously reported suppression of activator protein-1 (AP-1) and degradation of IL-2 by proteinases from P. gingivalis. In the present study, we have analyzed the effects of P. gingivalis on Jurkat T-cell signal transduction and subsequent IL-2 and CXCL8 expression. We found that CXCL8, but not IL-2, gene expression levels were significantly suppressed by viable P. gingivalis. Analysis of intracellular signaling revealed an inhibitory effect of P. gingivalis on c-Jun and c-Fos, but not NFκB (p50 and p65), NFAT or STAT5 expression. This inhibitory effect was not due to suppression of mitogen-activated protein kinase (MAPK) (p38, erk and JNK) gene expression, but was rather due to prevention of protein kinase C (PKC) and p38 phosphorylation, as demonstrated by western blot analysis. Furthermore, SOCS1 and SOCS3 expression levels decreased following treatment of Jurkat T cells with viable P. gingivalis. The results indicate that P. gingivalis is able to suppress inflammatory gene expression by targeting the activity of MAPK pathways in T cells, which was confirmed by using specific inhibitors of NF-κB, PKC, ERK, p38 and JNK.     

Detection of IL-5 and IL-1 receptor antagonist in bronchoalveolar lavage fluid in acute eosinophilic pneumonia

BACKGROUND: Acute eosinophilic pneumonia is an idiopathic cause of respiratory failure, characterized by very high numbers of alveolar eosinophils without significant blood eosinophilia. OBJECTIVE: The purpose of this study was to determine which cytokines are associated with acute eosinophilic pneumonia. METHODS: Soluble IL-1 type II receptor and the cytokines IL-1β, IL-1ra, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-α were measured in serum and in bronchoalveolar lavage fluid from two patients with acute eosinophilic pneumonia during both acute and convalescent phases. RESULTS: Compared with patients with adult respiratory distress syndrome, the patients with acute eosinophilic pneumonia had high bronchoalveolar lavage fluid levels of IL-5, IL-1ra, and soluble type II IL-1 receptor but not IL-1β, tumor necrosis factor-α>, IL-3, or granulocyte-macrophage colony-stimulating factor. Bronchoalveolar lavage fluid levels of IL-5 and IL-1ra fell after resolution of symptoms. In the serum of patients with acute eosinophilic pneumonia, IL-5 was not detectable, and IL-1ra was initially high but fell after corticosteroid treatment. CONCLUSION: Acute eosinophilic pneumonia is characterized by locally high levels of IL-5, IL-1ra, and soluble type II IL-1 receptor in the alveolar space. (J ALLERGY CLIN IMMUNOL 1996;97:1366-74.)     

The relationship between colonization and haemagglutination inhibiting and B cell epitopes of Porphyromonas gingivalis

Passive immunization with the monoclonal antibody 61BG1.3 selectively prevents colonization by Porphyromonas gingivalis in humans (Booth V, Ashley FP, Lehner T. Infect Immun 1996; 64:422-7). The protective MoAb recognizes the j3 component of the RI protease of P. gingivalis which is formed by proteolytic processing of a polyprotein precursor termed PrpRl. This subunit is both a haemagglutinin and an antigen which is recognized by sera from patients with periodontitis. In this study the relationship was investigated between a colonization epitope which is recognized by the MoAb 61BG1.3, a haemagglutinating and B cell epitope which are recognized by sera from patients with periodontitis. B cell epitopes were mapped by Western blotting with a series of truncated recombinant polypeptides spanning the adhesion domain within residues 784–1130 of PrpRl and by ELISA using a panel of synthetic peptides spanning the same sequence. The epitope which is recognized by the protective MoAb was mapped within residues 907–931 of PrpRl, while serum responses of patients were directed predominantly to the adjacent carboxy-terminal sequence within residues 934–1042. The haemagglutinating epitope was mapped to residues 1073–1112. In view of our previous findings that the MoAb 61BG1.3 prevents colonization of P. gingivalis in vivo and inhibits haemagglutination, these two epitopes may be in proximity in the native protein. Active or passive immunization strategies which target the protective or haemagglutinating epitopes of the adhesion domain of PrpRl may provide a means of preventing infection with P. gingivalis.     

Transition metal ions induce carnosinase activity in PepD-homologous protein from Porphyromonas gingivalis

Aminoacylhistidine dipeptidase (EC 3.4.13.3; also Xaa-His dipeptidase, carnosinase, or PepD) catalyzes the cleavage and release of an N-terminal amino acid, which is usually a neutral or hydrophobic residue, from an Xaa-His dipeptide or degraded peptide fragment. PepD enzyme is found extensively in prokaryotes and eukaryotes, and belongs to the metallopeptidase family M20, a part of the metallopeptidase H (MH) clan. Carnosine is a naturally occurring dipeptide (β-alanyl-l-histidine) present in mammalian tissues that has protective functions in addition to anti-oxidant and free-radical scavenging roles. During bacterial infections, degradation of l-carnosine via carnosinase or PepD-like enzymes may enhance the destructive potential of bacteria, resulting in a pathological impact. This process has been proposed to act in an anti-oxidant manner in vivo. In the present study, the recombinant PepD protein encoded by Porphyromonas gingivalis TDC60 pepD was generated and biochemically characterized. In addition, a recombinant dipeptidase enzyme was found to function not only as an alanine-aminopeptidase, but also as a carnosinase. Furthermore, when carnosine was used as substrate for PepD, the transition metals, Mn²⁺, Fe²⁺, Co²⁺, and Ni²⁺ stimulated the hydrolyzing activity of rPepD with β-alanine and l-histidine. Based on its metal ion specificity, we propose that this enzyme should not only be termed l-aminopeptidase, but also a carnosinase.     

Role of the hemin-binding protein 35 (HBP35) of Porphyromonas gingivalis in coaggregation

Hemin-binding protein 35 (HBP35) in Porphyromonas gingivalis is one of the outer membrane proteins and has been reported to be a non-fimbrial coaggregation factor. In this study, a P. gingivalis HBP35-deficient mutant (MD774) was constructed from wild-type strain FDC381 by insertion mutagenesis in order to provide a better understanding of this protein's role in coaggregation. The intact cells and vesicles in FDC381 were found to have strong aggregation activities with Gram-positive bacteria. But neither the vesicles nor the intact cells showed aggregation activity in MD774. In addition, MD774 reduced autoaggregation activity. Immunoblot analysis of MD774 showed the presence of a non-maturated 45-kDa fimbrillin protein. Electron microscopy showed that the MD774 had no long fimbriae on the cell surface. Arg- and Lys-gingipain activity in MD774 was significantly decreased, compared with FDC381. Real-time RT-PCR demonstrated a significant reduction in the expression of gingipain-associated genes rgpA, rgpB, and kgp. In conclusion, we suggest that the reduction in coaggregation was caused by the combined reduction of a variety of molecules, including HBP35, gingipains, and fimbriae. Our results suggest that the HBP35 protein directly influences not only coaggregation as an adhesion molecule but also indirectly influences the expression of other coaggregation factors.     

慢性肾炎患者治疗前后血清IL-2、IL-6和TNF-α检测的临床意义

目的：探讨了慢性肾炎患者治疗前后血清IL-2、IL-6和TNF-α水平的变化及临床意义。方法：应用放射免疫分析对32例慢性肾炎患者进行了血清IL-2、IL-6和TNF-α水平测定,并与35名健康人作比较。结果：慢性肾炎在治疗前血清IL-6和TNF-α水平均非常显著的高于正常人组（P〈0.01）,而IL-2则显著的低于正常人组（P〈0.01）。经中西医结合治疗3个月后与正常人组比较仍有显著性差异（P〈0.05）。结论：检测慢性肾炎患者血清IL-2、IL-6和TNF-α水平的变化对观察病情及预后判定均具有重要的临床价值。     

Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains

Porphyromonas gingivalis is highly implicated in the pathogenesis of periodontitis, which is characterized by the destruction of periodontal connective tissues and the supporting alveolar bone. Receptor Activator of NF-kappaB Ligand (RANKL) stimulates bone resorption, whereas osteoprotegerin (OPG) blocks its action, and this bi-molecular system is implicated in periodontitis. The aim of this work was (a) to investigate the regulation of RANKL and OPG gene expression in human periodontal ligament (PDL) cells and gingival fibroblasts (GF), in response to P. gingivalis culture supernatants, by quantitative real-time PCR and (b) to attempt to identify putative virulence factors involved in this process. The results indicated that P. gingivalis induced RANKL and reduced OPG mRNA expression by the studied cells, resulting in an increased RANKL/OPG expression ratio. Heat-inactivation of P. gingivalis resulted in significant reduction of RANKL mRNA expression. A Lys-gingipain mutant strain did not affect, whereas an Arg-gingipain mutant strain further enhanced RANKL mRNA expression, compared to their parental wild-type strain. In conclusion, P. gingivalis up-regulates the RANKL/OPG expression ratio in GF and PDL cells, denoting an enhanced osteoclastogenic potential by the cells. The component mainly responsible for RANKL induction appears to be proteinaceous, and it may be regulated by the Arg-gingipains.     

急性白血病患者IL-6,TNF-α和sIL-6R含量及其与白血病负荷的相关性

应用生物学检则法,ELISA法和间接免疫荧光法分析了24例急性白血病患者外周血IL-6,sIL-6R和TNF-α的含量及其与白血病细胞负荷的相关性.结果显示:(1)急性白血病患者外周血IL-6,sIL-6R及TNF-α水平明显升高,其中急性B淋巴性白血病(B-ALL)的IL-6,sIL-6R及急性T淋巴性白血病(T-ALL)的TNF-α升高尤为明显;(2)B-ALL的IL-6,TNF-α及T-ALL的TNF-α水平与白血病细胞负荷有着较好的正相关性;而sIL-6R水平与白血病细胞负荷则无明显的相关.由此表明不同类型的白血病存在不同的有利于肿瘤细胞生长的生物因子微环境,这些生物因子及其受体的异常表达与白血病的发生发展相关.     

Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass

Cardiac surgery with cardiopulmonary bypass (CPB) leads to a systemic inflammatory response with secretion of cytokines (e.g. IL-6, TNF-alpha, IL-1 beta and sIL-2R). The objective of the following study was to investigate in vitro and in vivo cytokine responses and white blood cell counts (WBC) of patients with high versus low cytokine secretion after a coronary artery bypass grafting (CABG) procedure. Twenty male patients undergoing elective CABG surgery with CPB under general anaesthesia were enrolled in the study. On the day of surgery (postoperatively), serum levels of TNF-alpha and IL-1 beta were significantly higher in patients of the high IL-6 level group compared to the respective values in the patient group with low IL-6 levels. The inter-individual differences in IL-6 release in patients undergoing CABG surgery with CPB were accompanied by differences in the release of other cytokines, such as TNF-alpha, IL-1 beta and sIL-2R. To understand whether genetic background plays a role in influencing cytokine plasma levels under surgical stress, we examined the distribution of polymorphic elements within the promoter regions of the TNF-alpha and IL-6 genes, and determined their genotype regarding the BAT2 gene and TNF-beta intron polymorphisms. Our preliminary data suggests that regulatory polymorphisms in or near the TNF locus, more precisely the allele set 140/150 of the BAT2 microsatellite marker combined with the G allele at -308 of the TNF-alpha gene, could be one of the genetic constructions providing for a less sensitive response to various stimuli. Our results suggest: (1) close relationships between cytokine release in the postoperative period, and (2) inter-individually varying patterns of cytokine release in patients undergoing CABG surgery with CPB.     

姜黄素治疗大鼠脑出血后血清IL-6、IL-1β、TNF-α变化的实验研究

目的 本研究旨在探索大鼠脑出血(intracerebral hemorrhage,ICH)用姜黄素治疗后血清IL-6、IL-1β、TNF-α变化情况,评价姜黄素在治疗脑出血中的抗炎价值,从而为临床应用姜黄素治疗脑出血提供科学的实验数据.方法 24只健康雄性成年SD大鼠,单纯随机分为术前正常对照组(A组),脑出血姜黄素治疗组(B组),脑出血空白对照组(C组),假手术组(D组),每组6只大鼠.立体定位下右侧基底节注射胶原酶法制备大鼠脑出血模型.于建模成功后6h、24h、48h、3d、5d、7d、14d,给各组大鼠尾静脉取血测IL-6、IL-1β、TNF-α.将B组与C组、D组的IL-6、IL-1β、TNF-α值行两样本t检验比较,P＜0.05为差异有统计学意义.结果 B组的神经生物学评分较相应时期的C组低,较相应时期的D组高,差异有统计学意义.B组的血清IL-6、IL-1β、TNF-α水平在术后6h即升高,3d达最高水平,随后开始逐渐恢复,且各个时期的血清IL-6、IL-1β、TNF-α水平均较同时期C组低,较同时期的D组高,差异均有统计学意义.结果 姜黄素能加快大鼠脑出血后血清炎症因子的吸收,对大鼠脑出血有抗炎作用.     

铁缺乏孕妇外周血单个核细胞IL-2、IL-6分泌水平研究

目的探讨铁缺乏及不同补铁浓度对孕妇外周血单个核细胞（PBMC）IL-2、IL-6分泌水平的影响,为临床补铁提供理论依据。方法孕妇血肝素抗凝,分离PBMC。给予LPS或PHA刺激后,用酶联免疫吸附法（ELISA）检测不同铁浓度环境下健康及铁缺乏孕妇PBMC的IL-2、IL-6分泌水平。结果体外试验表明：给予LPS或PHA刺激后,铁缺乏患者PBMC的IL-2分泌水平低于健康孕妇平均水平,IL-6高于健康孕妇平均水平;不同补铁浓度对IL-2分泌水平无影响,但IL-6分泌水平有所提高。结论孕期应该注重含铁食物的摄入,平衡膳食,预防因铁营养缺乏而导致的免疫功能下降;铁缺乏孕妇适量补铁有利于提高IL-6的分泌水平,促进机体造血功能的改善与恢复。     

Porphyromonas gingivalis induces RANKL in bone marrow stromal cells: involvement of the p38 MAPK

Periodontitis is a bacterially-induced oral inflammatory disease that is characterised by tissue degradation and bone loss. Porphyromonas gingivalis is a gram negative bacterial species highly associated with the pathogenesis of chronic periodontitis. Receptor activator of nuclear factor-kB ligand (RANKL) induces bone resorption whilst osteoprotegerin (OPG) is a decoy receptor that blocks this process. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the production of prostaglandin (PGE)_2, which is a major inflammatory mediator of bone resorption. Mitogen-activated protein kinases (MAPK) are intracellular signalling molecules involved in various cell processes, including inflammation. This study aimed to investigate the effect of P. gingivalis on MAPKs and their involvement in the regulation of RANKL, OPG and COX-2 expression in bone marrow stromal cells. P. gingivalis challenge resulted in the phosphorylation of primarily the p38 MAPK. RANKL and COX-2 mRNA expressions were up-regulated, whereas OPG was down-regulated by P. gingivalis. The p38 synthetic inhibitor SB203580 abolished the P. gingivalis-induced RANKL and COX-2 expression, but did not affect OPG. Collectively, these results suggest that the p38 MAPK pathway is involved in the induction of RANKL and COX-2 by P. gingivalis, providing further insights into the pathogenic mechanisms of periodontitis.     

Plasma concentrations of TNF-α and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease

Tumour necrosis factor alpha (TNF-α) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-α receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins.
The aim of the study was to establish factors associated with plasma concentrations of TNF-α and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-α, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 ( AMPD1 , C34T) and adenosine deaminase ( ADA , G22A), were analyzed.
Plasma concentrations of TNF-α, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-α, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-α and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-α, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-α or its receptors.
In conclusion, the concentrations of TNF-α, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-α and its receptors.     

慢性前列腺炎患者治疗前后血清TNF-α、IL-6和IL-8检测的临床意义

目的：探讨了慢性前列腺炎患者治疗前后血清TNF-α、IL-6和IL-8水平的变化及意义。方法：应用放射免疫分析对42例慢性前列腺炎患者进行了血清TNF-α、IL-6和IL-8检测,并与35名正常健康人作比较。结果：慢性前列腺炎患者在治疗前血清TNF-α、IL-6和IL-8水平均非常显著地高于正常人组（P〈0.01）,经综合治疗后2周,除TNF-α水平与正常人比较无差异外,血清IL-6和IL-8水平与正常人比较仍有显著性差异（P〈0.05）。结论：血清TNF-α、IL-6和IL-8可能以不同的方式参与了慢性前列腺炎的发病,其检测对了解病情、指导治疗具有重要的临床价值。     

B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis

The up-regulation of the B7-H1 receptors in host cells might influence the chronicity of inflammatory disorders that frequently precede the development of human cancers. B7-H1 expression has been detected in the majority of human cancers, leading to anergy and apoptosis of activated T cells, and enabling tumor cells to overcome host response. Porphyromonas gingivalis (P. gingivalis), a putative periodontal pathogen, is an etiologic agent of periodontitis and expresses a variety of virulence factors. In this study, the expression of B7-H1 and B7-DC receptors on squamous cell carcinoma cells SCC-25 and BHY and primary human gingival keratinocytes (PHGK) was analyzed after infection with two virulent P. gingivalis strains in vitro. After 48 h, the cells were stained with antibodies for human B7-H1 and B7-DC and further analyzed by flow cytometry. RNA was extracted and gene expression of B7-H1 or B7-DC was quantified by real time PCR. After infection with P. gingivalis, both B7-H1 and B7-DC receptors were up-regulated.The mean fluorescence intensity (MFI) increased from 4.5 to 9.9 (B7-H1) and from 6.9 to 15.0 (B7-DC) (p < 0.05, respectively) in SCC-25 cells. PHGK showed an increase from 4.8 to 12.4 (B7-H1) and from 5.5 to 15.6 (B7-DC) (p < 0.05, respectively). Streptococcus salivarius K12, a commensal bacterium, caused no up-regulation. After 24 h, the expression of B7H1 and B7-DC mRNA in infected cells, normalized to GAPDH and in relation to non-infected cells, was 6.4 fold (B7-H1) and 8.6 fold (B7-DC) higher. In PHGK B7-H1/DC mRNA expression increased 8.2 fold (B7-H1) and 5.9 fold (B7DC) (p < 0.05) respectively. The results of the study demonstrate that in contrast to S. salivarius K12 virulent P. gingivalis strains are able to induce the expression of the B7-H1 and B7-DC receptors in squamous carcinoma cells and human gingival keratinocytes, which might facilitate immune evasion by oral cancers.     

IL-2对中子照射后肠上皮细胞生长和凋亡的影响及其机制

目的:观察中子照射对体外培养的IEC-6细胞生长的影响及IL-2对其损伤后增殖和恢复的作用,并进一步探讨IL-2调节受照射肠上皮细胞生长的相关机制。方法:单独用IL-2(1×105U/L)或同时施加JAK1激酶阻断剂(A77-1726)处理受4Gy中子照射的IEC-6细胞,并于照后10、15、30min和1、3、6、12、24、48及72h,用MTT比色法和流式细胞术检测受照射后IEC-6细胞的增殖活力和死亡方式的改变。以免疫细胞化学染色和Western blot检测IEC-6细胞上IL-2Rβ的表达和JAK1活化情况。结果:4Gy中子照射后24h,IEC-6细胞的增殖活力明显降低;而IL-2处理组该细胞的增殖活力有显著提高(P<0.05)。受中子照射的IEC-6细胞经IL-2作用24h,其凋亡率明显降低(P<0.05),而坏死率变化不明显。以IL-2刺激中子照射的IEC-6细胞后,于10及15min可见JAK1发生明显磷酸化活化,24h时IL-2Rβ的表达明显增多。同时应用A77-1726和IL-2处理受中子照射的IEC-6细胞后,其增殖活力明显低于单纯IL-2处理组。结论:IL-2可促进受中子照射的IEC-6细胞增殖,具有抗辐射作用。IL-2Rβ和JAK1活化参与了IL-2对中子损伤的IEC-6细胞生长的调控。     

N-乙酰半胱氨酸治疗肺炎患儿全身炎症反应综合征的临床研究

目的探讨N-乙酰半胱氨酸（NAC）在小儿肺炎治疗及预防全身炎症反应综合征（SIRS）中的作用。方法将90例肺炎伴SIRS患儿随机分为治疗组和对照组,治疗组常规治疗结合富露施（乙酰半胱氨酸颗粒）口服或胃管注入,对照组常规治疗结合复方甘草合剂治疗。于治疗前和治疗后第6天查血清中白介素-1（IL-1）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、ALT、AST和CR的浓度,并观察肺炎相关症状和体征变化。结果治疗组治疗整体有效率为91.1%,对照组治疗整体有效率为75.6%,治疗组疗效高于对照组（P〈0.05）;住院天数较对照组少;临床分期Ⅰ期、Ⅱ期治疗组有效率与对照组相同,Ⅲ期、Ⅳ期治疗有效率高于对照组;Ⅴ期两组患儿均疗效欠佳,死亡率均为100%;两组治疗后血ALT、CR、IL-6、TNF水平较治疗前均明显下降,但治疗组较对照组下降更为明显（P〈0.01）。结论早期使用NAC可降低炎症反应对各器官的损伤,改善肝肾功能,缩短肺炎病程和提高治愈率;NAC可能通过调控IL-6和TNF-α等炎症因子水平,一定程度上干预肺炎患儿SIRS向多脏器功能不全综合征（MODS）进展,减少MODS的发生。     

Inverse regulation of interleukin-6 (IL-6) and IL-6 receptor in histamine deficient histidine decarboxylase-knock-out mice

Interleukin-6, a multifunctional cytokine upon binding to its receptor on hepatocytes regulates production of acute phase proteins involved in local and systemic inflammation. Gene expression and biosynthesis of IL-6 and its receptor (IL-6 R/gp130) is under complex regulation. Histamine, in addition to its principal role in immediate type hypersensitivity has been described to modulate IL-6 production and expression of IL-6 receptor. In this study, the IL-6 and IL-6 receptor expression was examined in histamine deficient histidine decarboxylase (HDC) knock-out mouse model. Our data suggest that in histamine deficient mice the inducibility of IL-6 is significantly reduced, whilst more IL-6 receptor/gp130 mRNA expresses in the liver than in wild type (HDC^+/+) mice. These in vivo findings confirm earlier in vitro results and emphasize the efficacy of antihistamines in local IL-6 related processes.