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The aims of this study were to describe hormonal profiles, cytokine production and Fc-gamma receptor (Fcgamma-R) distribution in male lupus patients in Taiwan, and to look for any differences between our patients and normal individuals. Sixteen newly diagnosed and untreated male lupus patients were studied. Hormonal profiles were determined by radioimmunoassay. Interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra) production from both monocytes and neutrophils was determined by ELISA and murine thymocyte proliferation assay. The FcgammaR distribution on both monocytes and neutrophils was detected by flow cytometer. There were no significant differences in FSH, LH, testosterone, oestradiol, and beta-HCG blood levels in male lupus patients compared with normal individuals; however, the prolactin level in lupus patients was significantly higher than in normal individuals. Furthermore, there was no difference in IL-1 and IL-1ra production from both monocytes and neutrophils among male and female lupus patients, and normal individuals. Male lupus patients have a significantly lower FcgammaRII distribution on both monocytes and neutrophils when compared with female lupus patients and normal individuals. It was concluded that the high prolactin level and low FcgammaR distribution may play a role in the pathogenesis and prognosis of male lupus.

Cytokines, such as interleukin-1 (IL-1), may play a key role in the pathogenesis of IgA nephropathy (IgAN). This study was conducted to evaluate the effects of IL-1 receptor antagonist (IL-1ra) in the treatment of a spontaneously occurring experimental IgAN in established phase. ddY mice (12/group) were injected twice daily with 3 mg/kg of IL-1ra, intraperitoneally, for 8 consecutive weeks. The placebo mice were injected with saline only. As normal controls, ddY mice, which were not treated with IL-1ra or saline, were killed at 6 weeks of age. Results showed a significant reduction of proteinuria in the IL-1ra-treated mice, compared with saline-treated mice (urinary albumin/creatinine, 0.24 +/- 0.04 v 0.39 +/- 0.03, P < 0.001). A significant improvement of renal 51Cr-EDTA (ethylenediaminetetra-acetic acid) clearance was observed in the IL-1ra-treated mice (t1/2, 12 +/- 2.7 minutes, compared with saline-treated mice 25 +/- 2.0 minutes, P < 0.001). Similarly, serum levels of creatinine (1.0 +/- 0.4 v 2.4 +/- 0.3 mg/dL, P < 0.001) and urea nitrogen (46 +/- 6 v 58 +/- 2 mg/dL, P < 0.01) were significantly lower in IL-1ra-treated mice than in saline-treated mice. In renal tissue studies, the IL-1ra-treated mice exhibited significantly decreased mesangial cell proliferation, compared with saline-treated mice (P < 0.001), as shown by light and electron microscopy. In addition, the IL-1ra-treated mice showed significantly lower glomerular expression of collagen type IV, fibronectin, laminin, and IL-6 (P < 0.001) than saline-treated mice, although they still showed higher glomerular expression of collagen type IV (P < 0.01), fibronectin (P < 0.01), laminin (P < 0.001), IL-1 (P < 0.001), and IL-6 (P < 0.01) than did normal control mice. Meanwhile, glomerular C3 deposition was significantly lower in IL-1ra-treated mice than in saline-treated mice (P < 0.001). These findings indicate that IL-1ra partially prevented the progression of spontaneously occurring IgAN in this experimental model. Data from these experiments also confirm the pathogenic effects of IL-1 in the established phase of IgAN in ddY mice.

Interleukin-1 (IL-1) is thought to play an important role in the immunopathology of systemic lupus erythematosus (SLE). IL-1 receptor antagonist (IL-1ra) exhibits a dose-responsive inhibition of IL-1 effects, and Fcr receptors play a key role in IL-1ra production. To clarify the relationship between IL-1, IL-1 receptor antagonist (IL-1ra) production, and Fcr receptors in SLE, fifteen untreated lupus patients (9 females and 6 males) were evaluated. IL-1 and IL-1ra production from both monocytes and neutrophils was determined by both a murine thymocyte proliferation assay and ELISA. The expression of Fcr receptors on both monocytes and polymorphonuclear cells was measured by flow cytometry. There was no significant difference between IL-1 beta and IL-1ra production from ex vivo monocytes between lupus patients and normals. However, serum IL-1ra was significantly higher in lupus patients than in normals. The expression of FcrRII (CD32) on monocytes was lower in lupus patients than in normals. There was no correlation between the expression of FcrRII and the serum immune complexes; the production of IL-1ra and the expression of CD32, serum immune complex levels, and serum IgG. Both serum IL-ra and the production of IL-1ra had no correlation to SLEDAI, C3, C4, C1q, or ESR. These observations suggest that although IL-1 and IL-1ra may not play a major role in the initiation of pathogenesis of lupus, the low FcrRII expression in lupus may reflect low immune complex clearance and contribute to disease pathogenesis.

The increasingly complex cytokine network involves both positive and negative regulatory pathways. Natural inhibitors of cytokines are of great importance both as analytical tools and as potential therapeutic agents. Interleukin-1 (IL-1) inhibitory bioactivity including a specific receptor antagonist of IL-I (IL-1ra) has been described both in cultured cell supernatants and in human body fluids. In the current studies, the cDNA of IL-1ra from human monocytes was obtained by the techniques of mRNA isolation and reverse transcription/polymerase chain reaction (RT/PCR). The IL-1ra cDNA/pET-15b was transfected into DE3 cells and the recombinant protein expressed. The purified protein was demonstrated as a single band with molecular mass of 20 KD by SDS-PAGE; it had strong IL-1 inhibitory activity. This IL-1 inhibitor competed with IL-1 for their receptor as assessed by flow cytometer. The existence of this naturally occurring specific cytokine receptor antagonist may lead to a different perspective of the cytokine network. The availability of this recombinant IL-1 receptor antagonist allows us to test its role on the cytokine network, and on possible disease modification.

Dengue hemorrhagic fever-dengue shock syndrome, the most severe manifestation of an acute dengue virus (DV) infection, is endemic in Southeast Asia. Antibody-dependent enhancement of DV growth in mononuclear phagocytes is thought to be the mechanism whereby preexisting dengue antibodies confer excess risk for this outcome. Interleukin-1 (IL-1) may play an important role in the pathogenetic mechanisms that cause dengue fever and shock. It was shown that both IL-1 and tumor necrosis factor-alpha are secreted from monocytes within 4 h after DV infection. However, there was no increase in IL-1 secretion by virus-stimulated monocytes from dengue fever patients compared with healthy controls. Significant amounts of IL-1 were secreted by DV-infected monocytes in the presence of aggregated immunoglobulin or immune complexes. In addition, a new 600-kDa IL-1 inhibitor from the supernatants of DV-infected monocytes was identified. This inhibitor may cause immunosuppression and influence the process of DV infection.