Long-term follow-up of patients with tuberculosis as a complication of tumour necrosis factor (TNF)-alpha antagonist therapy: safe re-initiation of TNF-alpha blockers after appropriate anti-tuberculous treatment.

This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.     

Circulating levels of sTNFR and discrepancy between cytotoxicity and immunoreactivity of TNF-α in patients with visceral leishmaniasis

Objectives To study the influence of soluble tumour necrosis factor (TNF) receptors (sTNFR) on bioactivity and immunoreactivity of TNF-α in patients with visceral leishmaniasis (Kala-azar) and to examine the association between circulating levels of sTNFR type I and type II with clinical manifestations of the disease.
Methods   Ten patients with Kala-azar were enrolled. Plasma samples for TNF-α and sTNFR were obtained on days 0, 7 and 21–28 of antimonial therapy. Bioactivity of TNF-α was measured by cytotoxicity to L-929 cells and immunoreactivity by enzyme-linked immunosorbent assay (ELISA). sTNFR-I and sTNFR-II were measured by ELISA.
Results   Measured by ELISA, TNF-α was detected at baseline in all patients (range from 22.3 to 163 pg/mL) and showed a linear decline over time on therapy ( r  = −0.49, P  = 0.007). In contrast, when measured by cytotoxicity assay, TNF-α was detected in only one patient at baseline (193 pg/mL) and in four patients at the end of therapy (38.7, 95, 133 and 232 pg/mL) and there was no linear association between TNF-α and duration of therapy ( r  = −0.18, P  = 0.45). sTNFR-I and sTNFR-II were detected in all patients before therapy. There was a strong positive correlation between plasma concentrations of sTNFR-I and sTNFR-II ( r  = 0.8, P  = 0.006). Levels of sTNFR-I and sTNFR-II declined exponentially with time on therapy.
Conclusions   We concluded that sTNFR-I and sTNFR-II are related to disease activity in patients with Kala-azar and that these circulating receptors may interfere with the biological activity of TNF-α in patients with Kala-azar.     

Endogenous Adenosine Down-Modulates Mid-Trimester IntraAmniotic Tumor Necrosis Factor-α Production

Problem  To determine whether adenosine in amniotic fluid down-regulates pro-inflammatory cytokine production.
Method of study  Mid-trimester amniotic fluid from 21 women was incubated ex vivo in the presence or absence of human adenosine deaminase, the enzyme that irreversibly degrades adenosine. After 24 hr, supernatants were assayed by ELISA for tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10. Clinical parameters were obtained after completion of laboratory testing.
Results  Inclusion of adenosine deaminase resulted in a median increase in TNF-α production from 0.9 to 7.3 pg/mL ( P  = 0.0014). IL-6 production exhibited a non-significant median increase from <2.0 to 53.0 pg/mL ( P  = 0.0780). Median IL-10 production increased slightly from a median of <0.2 to 1.3 pg/mL. Adenosine deaminase-stimulated TNF-α production was proportional to parity and unrelated to gestational age, time of delivery, maternal age or indication for amniocentesis.
Conclusion  Adenosine deaminase treatment increases TNF-α production by ex vivo -cultured amniotic fluid. Adenosine contributes to immune modulation in the amniotic cavity.     

Is TNF-α a prognostic factor in patients with sepsis?

Objective: To determine tumor necrosis factor-α (TNF-α) levels in a prospective study in 58 hospitalized patients in a department of internal medicine (63 episodes, 29 in immunocompromised patients) during a 7-month period.
Method: Patients fulfilling the following criteria were included: clinical evidence of acute infection, temperature >38.2°C, tachycardia >90 beats/min, tachypnea >20 breaths/min. Samples were taken from day 1 up to day 13 after an infection was diagnosed, and TNF-α was determined by enzyme immunoassay.
Results: In 29 episodes (46.0%) the infection was microbiologically documented. The median of the TNF-α levels in the Gram-negative episodes was significantly higher than that in the Gram-positive episodes ( p =0.002). Thirteen of 63 episodes (20.6%) had a fatal outcome. With respect to all measured values, the non-survivors had a significantly higher median of TNF-α levels than the survivors ( p =0.0001). There was, however, great interpatient and intrapatient variability in TNF-α levels; thus, no unequivocal correlation between TNF-α and outcome could be documented.
Conclusions: Our data indicate that the influence of the infecting organism on TNF-α kinetics is less pronounced than that of the underlying disease.     

Maternal Circulating TNF-α Levels are Highly Correlated with IL-10 Levels, but not IL-6 and IL-8 Levels, in Women with Pre-Eclampsia

Problem  Several lines of evidence have shown that maternal cytokine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-10 were altered in women with pre-eclampsia (PE) compared to those from normal pregnancies. In this study, we determined whether these cytokine levels are correlated before and after delivery in patients with PE.
Method of study  Venous blood was obtained from 50 women diagnosed with severe PE at the time of admission and 24 hr after delivery. Plasma concentrations for TNF-α, IL-6, IL-8, and IL-10 were measured by ELISA.
Results  There were no statistical differences for maternal levels of TNF-α, IL-6, IL-8, and IL-10 before and 24 hr postpartum. TNF-α and IL-10, but not IL-6 and IL-8, levels were significantly correlated before and 24 hr after delivery: TNF-α: y  = 19.963 + 0.953* x ; r ² = 0.924; IL-10: y  = 10.521 + 1.113* x ; r ² = 0.984, P  < 0.001, respectively. Furthermore, TNF-α levels were correlated with IL-10 levels, but not with IL-6 and IL-8 levels.
Conclusion  The correlation patterns of TNF-α with IL-10 and TNF-α with IL-6 and IL-8 suggest disparity in functional regulations between these cytokines in maternal circulation in PE.     

Anti-TNF Treatment of Baboons with Sepsis Reduces TNF-α, IL-6 and IL-8, but not the Degree of Complement Activation

The activation of complement and the release of TNF-α, IL-6 and IL-8 are important pathogenic factors behind organ dysfunction in sepsis. The aim of this study was to determine whether infusion of anti-TNF antibodies alters complement activation and plasma concentrations of pro-inflammatory cytokines at high doses of Escherichia coli . Six baboons received intravenously 2 × 10⁹ live E. coli bacteria per kg body weight (group 1), in addition five received pretreatment with 1 mg per kg body weight anti-TNF antibodies (group 2), and seven received 5 × 10⁸ live E. coli bacteria per kg body weight (group 3). Two hours after the start of infusion of the bacteria, plasma concentrations of C3 activation products, C5a and the terminal SC5b-9 complement complex were increased in groups 1 and 2 ( P  < 0.05), but there was no significant difference between the groups. At 2 h the levels of TNF-α, IL-6 and IL-8 were lower in group 2 compared with group 1 ( P  < 0.05). In group 2 compared with group 1 the TNF-α concentrations were, however, higher at 4, 8 and 24 h. The explanation for this phenomenon is probably that TNF-α binds to the anti-TNF antibody complex and is released slowly after it has been bound. The study showed that infusion of anti-TNF antibodies reduced the concentrations of TNF-α, IL-6 and IL-8, without any detectable influence on complement activation.     

Tumor Necrosis Factor-α-Associated Mechanisms Affecting the Embryonic Response to Cyclophosphamide

Problem  We have previously shown that TNF-α^−/− embryos are more sensitive to the exposure to cyclophosphamide (CP) compared with TNF-α^+/+ embryos; however, the underlying mechanisms are not fully understood. Thus, in our present study, we tried to identify those molecules that might be responsible for the protective effect of the cytokine.
Method of study  CP-treated TNF-α^−/− and TNF-α^+/+ embryos were analyzed for changes in apoptosis by TUNEL and flow cytometry, while cell proliferation was analyzed by BrdU incorporation. The expression of Bax, bcl-2, p53, the p65 subunit of NF-κB and IκBα was assessed by Western blotting and immunohistochemistry.
Results  CP-treated TNF-α^−/− embryos exhibited a more profound decrease in their weight, which was accompanied by an earlier appearance of cellular damage and apoptotic cells and an earlier decrease in cell proliferation in the embryonic brain compared with TNF-α^+/+ embryos. Also, an increased percentage of Bax-positive cells and a decreased percentage of bcl-2-positive cells were detected in TNF-α^−/− embryos 48 hr after exposure, which were accompanied by a decreased percentage of p53-positive cells.
Conclusion  Our data implicate TNF-α to be involved in the protection of the embryo against CP teratogenicity, possibly via alteration in Bax, bcl-2 or p53 expression.     

Role of Tyrosine Kinase Enzymes in TNF-α and IL-1 Induced Expression of ICAM-1 and VCAM-1 on Human Umbilical Vein Endothelial Cells

The aim of this study was to analyse the potential roles of protein kinase enzymes in tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1) induced expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on human umbilical vein endothelial cells (HUVEC). The authors observed a marked increase in ICAM-1 and VCAM-1 expression on HUVEC stimulated for 24 h by TNF-α (10 ng/ml) or IL-1 (20 ng/ml). Pre-treatment of HUVEC for 30 min with protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A (10 μg/ml and 0.5 μg/ml, respectively) before stimulation with IL-1 did not affect the expression of these molecules. Similar results were observed with respect to VCAM-1 expression on HUVEC stimulated by TNF-α. In contrast, pre-incubation of HUVEC with PTK inhibitors prior to the addition of TNF-α significantly enhanced subsequent expression of ICAM-1, although spontaneous expression of ICAM-1 on unstimulated HUVEC was unaffected. Western blot analysis demonstrated a significant increase in phosphorylated tyrosine protein levels in HUVEC stimulated by TNF-α , and significantly lower levels of these proteins in TNF-α stimulated HUVEC pre-treated with PTK inhibitors. These results demonstrate that IL-1 induced ICAM-1 and VCAM-1 expression does not result from activation of PTK-dependent pathways. In the case of TNF-α induced responses, the selective co-stimulatory effect of this cytokine in combination with PTK inhibitors on ICAM-1 expression suggests a complicated intracellular pathway of TNF-α induced ICAM-1 expression, possibly involving down-modulation of increases in ICAM-1 by PTK enzymes.     

Do High and Low Tumour Necrosis Factor‐α Responders Exist in Dairy Cows?

A whole blood stimulation assay with Escherichia coli (O111:B4) endotoxin was established to measure the capacity of dairy cows to produce the proinflammatory cytokine tumour necrosis factor-α (TNF-α) ex vivo . Initially, a time- and dose-dependent study was carried out to find the optimal stimulation conditions for the TNF-α response. The TNF-α response peaked between 3 and 4 h at 38.5 °C. A dose in the range of 5–10 g of E. coli lipopolysaccharide (LPS)/ml whole blood was found to give the maximum TNF-α response. Thirty-eight Danish–Holstein dairy cows were investigated for their TNF-α responsiveness ex vivo in the periparturient period. Heparin-stabilized blood samples were collected seven times over a period of 4 months (weeks −3, −1, 2, 3, 5, 9 and 13 around calving) and stimulated with 5 g/ml of E. coli LPS. Indeed, fluctuations in the TNF-α responsiveness occurred over time. Moreover, the mean TNF-α responsiveness of 38 cows was found to be significantly increased ( P  < 0.001) in the weeks close to calving. However, in the more stabile physiological periods, some cows had a consistently low TNF-α response, whereas others had high a TNF-α response. We are currently investigating whether high and low TNF-α responders to E. coli LPS also exist in dairy cows in vivo . Moreover, the importance of TNF-α responsiveness ex vivo to dairy cows' susceptibility and clinical response to experimental E. coli infections in the udder is being investigated.     

Evaluation of tumor necrosis factor-α, interleukin-6 and C-reactive protein plasma levels as predictors of bacteremia in patients presenting signs of sepsis without shock

Objective: To evaluate the sensitivity of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) plasma measurement to detect bacteremia in patients presenting sepsis signs, and to evaluate the potential benefit of such measurement in terms of early antimicrobial therapy initiation.
Method: Plasma was obtained from 166 hospitalized patients for whom blood cultures were drawn for sepsis. Clinical data and antimicrobial therapies were noted. IL-6, TNF and C-reactive protein (CRP) were measured. The sensitivities of these markers were retrospectively compared with the accuracy of the attending physician in initiating empirical antimicrobial therapy. The setting was an 850-bed university hospital.
Results: Thirty-four bacteremias and 69 non-bacteremic infections were noted. In 63 others, no infection was documented. Median (range) IL-6 plasma levels in the three groups of patients were 462 (15–50 850), 189 (<15–38 300) and 91 (<10–13 750) pg/mL, respectively ( p <0.01). The corresponding TNF-α plasma levels were 37.5 (<15–2400), 15 (<15–240) and 15 (<15–200) pg/mL, respectively ( p <0.01). CRP plasma levels were 10.7 (<0.6–30.2), 10.3 (<0.6–34.4) and 7.3 (<0.6–20.9) mg/dL, respectively ( p =0.12). With respect to these three parameters, IL-6 and TNF-α appear better than CRP for predicting bacteremia. Clinical features resulted in starting empirical antimicrobial therapy in only 62% of the bacteremic patients. On the other hand, 68% of these bacteremic patients had high IL-6 plasma levels (>200 pg/mL). A combination of clinical features and high IL-6 levels would have permitted early treatment for 82% of the bacteremic patients.
Conclusions: IL-6 and TNF-α thus appear to be useful and earlier markers of bacteremia in septic patients. By contrast, CRP is neither sensitive nor specific in this setting.     

Incidences of Serious Infections and Tuberculosis among Patients Receiving Anti-Tumor Necrosis Factor-α Therapy

Purpose

Anti-tumor necrosis factor-alpha (TNF-α) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea.

Materials and Methods

We retrospectively studied patients who received anti-TNF-α therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-α therapy. Data concerning patient demographics, types of anti-TNF-α agents, concomitant immunosuppressive drugs use, and infection details were collected.

Results

A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohn''s disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results.

Conclusion

Serious infections with anti-TNF-α therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-α therapy, especially in countries with a high prevalence of TB.     

Recombinant Human Tumour Necrosis Factor-α (rhTNF-α) and rhTNF-α Analogue Enhance Amyloid Deposition in the Syrian Hamster

Tumour necrosis factor-α (TNF-α) is one of the cytokines that stimulate the production of serum amyloid A (SAA), the precursor of AA amyloid. The role of TNF-α in amyloidogenesis was investigated in experimental hamsters using purified recombinant human TNF-α (rhTNF-α) and rhTNF-α analogue different from the normal molecule by two amino acid substitutions. Daily injections of 1 μ g rhTNF-α resulted in elevated SAA levels but even in the presence of amyloid enhancing factor (AEF) no amyloid was deposited, indicating that apart from the AEF and one particular SAA stimulating factor an additional factor is needed to result in amyloid deposition. This factor is generated by repeated injections of E. coli lipopolysaccharide (LPS).
A single intraperitoneal injection of 12,5 μg or more of rhTNF-ä followed by seven daily subcutaneous injections of LPS resulted in enhanced amyloid deposition. Heat denaturation of rhTNF-α did abolish its AEF activity. The rhTNF-α analogue, having one-fifth of the cytotoxic activity of the normal rhTNF-α, showed a similar reduction in its SAA-inducing capacity and its amyloidogenicity. This suggests the AEF activity to be closely related to TNF-α activity. However, poly(I)poly(C) (a potent inducer of IL-6) also showed AEF activity, suggesting that not a single cytokine but rather a certain combination of different cytokines could be decisive in AA amyloidogenesis.     

Tuberculosis in children at Mbarara University Teaching Hospital,Uganda: diagnosis and outcome of treatment

Background

The diagnosis of tuberculosis in children is difficult particularly in HIV infected children. The poor outcome following antituberculosis treatment usually reported in HIV infected children might be due, in part, to other HIV-related chronic diseases wrongly diagnosed as TB.

Objective

The study examines the impact of HIV infection on the clinical features and diagnosis of children presenting with suspected tuberculosis in Mbarara University Teaching Hospital. It also examines the effect of various factors on the outcome of anti-TB treatment.

Methods

Children presenting with suspected TB were prospectively enrolled. Clinical data were recorded and investigations included Mantoux test, chest X-ray, HIV test and Z-N staining of various specimens for AAFBs where available. Patients were treated with standard, short-course anti-TB therapy, and followed-up for six months. They were then classified as “good outcome” if they improved and “poor outcome” if they deteriorated or died whilst on treatment.

Results

A total of 128 children were enrolled over an 18-month period. Four patients (3.1%) had a diagnosis of confirmed TB, 82 (64.1%) with “probable TB” and 42 (32.8%) with “suspected TB”. Of 88 patients tested 43 (48.9%) were HIV positive. HIV positive patients had a higher frequency of failure to thrive, digital clubbing, enlarged lymph nodes and hepatomegaly; and a lower frequency of positive Mantoux tests. HIV positive patients were less likely to be classified as “confirmed or probable TB” (χ² = 5.02, p = 0.025). Fifty six patients had a good outcome, 12 had a poor outcome and 60 defaulted before completing six months of treatment. HIV positive children were more likely to have a poor outcome (relative risk = 9.58, 95% CI 1.32 – 69.46). A diagnosis of “confirmed or probable TB” was associated with a good outcome (relative risk for poor outcome = 0.14, 95% CI 0.05 – 0.36).

Conclusion

HIV positive children with suspected TB frequently have signs that suggest the presence of other diseases such as Lymphocystic Interstitial Pneumonitis (LIP) and chronic bronchiectasis; and are less likely to have a diagnosis of “probable or confirmed TB” after investigations. Patients with an uncertain diagnosis of TB are less likely to improve on anti-TB therapy.     

Urocortin Increases IL-4 and IL-10 Secretion and Reverses LPS-induced TNF-α Release from Human Trophoblast Primary Cells

Problem  As urocortin (Ucn) is a placental peptide belonging to the corticotrophin-releasing hormone (CRH) family that modulates immune function in other biological models, this study evaluated Ucn effects on cytokines secretion from cultured human trophoblast cells.
Method of study  Placentas were collected from normal term pregnancies after elective caesarean section, and primary trophoblast culture was prepared followed by the treatment of Ucn and/or CRH selective antagonists, antalarmin and astressin 2b. The anti-inflammatory cytokines IL-4 and IL-10 and the pro-inflammatory cytokine TNF-α were measured by ELISA.
Results  Urocortin treatment induced a significant and dose-dependent increase of IL-4 and IL-10, whereas it did not affect TNF-α secretion. When incubated in the presence of LPS, Ucn reversed LPS-induced TNF-α release from cultured trophoblast cells, an effect that was blocked by the CRH-R2 selective antagonist, astressin 2b.
Conclusion  Urocortin stimulates IL-4 and IL-10 secretion and reverses LPS-induced TNF-α release from trophoblast cells through action on CRH-R2 receptors, suggesting that this peptide may play a possible role as an anti-inflammatory agent.     

Progression of Articular Destruction and the Production of Tumour Necrosis Factor-α in Antigen-Induced Arthritis in Rabbits

We examined the progression of articular destruction and the production of tumour necrosis factor-α (TNF-α) in antigen-induced arthritis (AIA) in rabbits, i.e. flare-ups of inflammation induced by repeated intra-articular injections (single, twice and three times) of antigen. A marked progression of articular destruction and an infiltration of inflammatory cells in the synovium were observed with the increase in the number of antigen injections. An immunohistochemical analysis of the synovial lesions following three injections of antigen revealed that the lymphoid follicles consisted mainly of CD4⁺ T cells and IgG/IgM⁺ B cells. There were marked infiltrations of IgG⁺ plasma cells around the lymphoid follicles. In contrast, the production of TNF-α in the synovial fluid and the erythrocyte sedimentation rate (ESR), which is a marker of systemic inflammatory activity in rheumatoid arthritis, peaked at 6 h and 24 h, respectively, following the last injection of antigen. These values were also greater following the repeated injections of antigen compared with the single injection. The TNF-α was produced markedly in the joints at the onset of the flare-ups of arthritis following the repeated injections of antigen, and the elevation of the ESR and an acceleration of the inflammatory response in the synovium were observed with a concomitant progression of severe articular destruction, suggesting that the marked production of TNF-α at the time of flare-ups may be involved in the exacerbation of AIA in rabbits.     

Cyclosporin A does not Inhibit IL-lα-Induced Epithelial Cell IL-6 Secretion

Trauma and infection activated a murine mucosal IL-6 response in different ways: the IL-6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL-6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA-insensitive IL-6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exposed to Escherichia coli Hu734, interleukin-lα (IL-lα) and tumour necrosis factor a (TNF-α). The E. coli strain had been used for the in vivo experiments which led to this study, and IL-lα and TNF-α were likely to be released during infections and trauma. The secretion of IL-6 into the supernatants was compared between cells stimulated in the presence or absence of CsA. E. coli Hu734, IL-lα and TNF-α stimulated an IL-6 response in the two epithelial cell lines. The IL-lα-induced IL-6 response was rapid, and the secreted IL-6 levels were significantly higher than those induced by E. coli Hu734 or TNF-α. The IL-6 response to IL- lα was insensitive to CsA. By contrast, the IL-6 response to E. coli Hu734 and TNF-α was inhibited by CsA. These results demonstrated that the inhibitory effect of CsA depends on the stimulus triggering the IL-6 response. IL-lα may play a role in the induction of trauma-associated CsA-insensitive IL-6 secretion.     

Influence of Tumour Necrosis Factor-α on the Expression of Fc IgG and IgA Receptors, and Other Markers by Cultured Human Blood Monocytes and U937 Cells

The expression of Fc receptors for IgG (FcγR) and IgA (FcαR) and of various other antigens on the human monocytic cell line U937 and peripheral blood monocytes, under stimulation with human recombinant tumour necrosis factor-α (TNF-α) and other cytokines, was investigated by flow cytomelry. TNF-α, as well as interferon-γ (IFN-γ) or interleukin-6 (IL-6) had a significant up-regulating effect on U937 expression of FcγRI/CD64. Furthermore, the action of TNF-α was augmented by IL-6, and more evidently by IFN-γ. IFN-α alone had only a marginal effect, but was able to increase the TNF-α-driven FcγRI expression. In contrast to U937 cells, TNF-α did not enhance significantly FcγRI expression on human monocytes. Interestingly, on both U937 cells and monocytes. FcαR was augmented markedly by TNF-α. Furthermore, TNF-α induced the expression of HLA-DR and HLA-DP antigens on monocytes and U937 cells. The expression of FcγRII/CD32, FcγRIII/CD16. CD14, complement receptor type 1 (CR1/CD35). CR4 (CD11c/CD18), and MHC class-I antigens, was not influenced significantly by TNF-α. The results of this study show that TNF-α may act on human mononuclear phagocytes, alone or in combination with other cytokines, by modulating the expression of various cell-surface antigens.