Serum samples of 120 patients in different stages of chronic human immunodeficiency virus type 1 (HIV-1) infection, 11 patients with primary HIV-1 infection (PHI), and 49 HIV-1 seronegative homosexual men were analyzed for tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), and HIV-1 p24 antigen. Increased levels of IFN-alpha and TNF-alpha were found in some, but not all, cases with PHI. During progressing disease IFN-alpha occurred in serum with increasing frequency and concentration. Raised levels of TNF-alpha were found in all stages of chronic infection, but were less common in patients with AIDS than were raised levels of IFN-alpha. The levels of the two substances were not correlated. There was a correlation between IFN-alpha, but not TNF-alpha, and the occurrence of HIV-1 p24 antigen in serum. These results suggest that IFN-alpha and TNF-alpha are induced by different agents during HIV-1 infection. The findings would be consistent with the hypothesis that IFN-alpha and TNF-alpha are counteracting forces that have important down- and upregulatory effects, respectively, on HIV-1 replication in vivo.
The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.
Allergic rhinitis is a particularly good model for studies of cytokine production in vivo. In this study the occurrence of the cytokines IL-4, IL-5, IL-10 and IFN-gamma as well as the soluble receptor for IL-4 in nasal lavage fluids were assayed in 38 school children, with seasonal allergic rhinitis, and 19 healthy age-matched, non-atopic controls, using highly sensitive enzyme immunoassays. IL-4 levels in patients with seasonal allergic rhinitis were markedly increased in comparison with those in non-atopic controls or in atopic patients before the start of the pollen season. In controls, but not in the atopic patients, levels of IFN-gamma and IL-5 were significantly higher in specimens obtained during the pollen season than in those obtained outside the season. The IL-4/IFN-gamma ratios were significantly higher in atopic than in non-atopic subjects and further increased in atopic patients during the season. In addition to IL-4, elevated levels of IL-10 were observed in association with seasonal rhinitis. Following treatment with a topical steroid (budesonide) there was a statistically significant increase of the levels of soluble IL-4 receptor. These findings indicate that nonatopic and atopic individuals react to pollen exposure with distinct cytokine patterns in agreement with the Th1/Th2 concept. Topical steroids may possibly decrease inflammation by increasing the formation of soluble IL-4 receptor.
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