Inflammation and infection induce an acute phase response. The response is characterized by fever and production of interleukin-1 (IL-1). In the present study we evaluated the effects of interleukin-1 on Leydig cell function in primary culture. hCG-stimulated testosterone formation was markedly reduced by IL-1, with an ED50 of 1 U/ml. Basal testosterone production was slightly enhanced in the presence of low concentrations of IL-1, while high concentrations of IL-1 inhibited testosterone formation. Significant inhibition of hCG-stimulated testosterone formation was noted as early as 8 h after the addition of IL-1. IL-1 also inhibited hCG-stimulated cAMP formation, as well as 8-bromo-cAMP- and forskolin-stimulated testosterone synthesis. Furthermore, LH binding to Leydig cells was reduced by human IL-1. The inhibitory effects of IL-1 were reversed only partially by the addition of a cyclooxygenase inhibitor, indomethacin (0.1 mM), even though prostaglandin E2 formation was completely blocked. This indicates that the observed effects of IL-1 are not completely mediated by increased PGE2 formation. The present study suggests that IL-1 is a potent modulator of Leydig cell steroidogenesis. Decreased testosterone formation may modulate the immune response and contribute to the catabolic changes occurring during infection.
In reviewing the literature on the relationship between age and suscepti bility to virus infections it became clear that the so-called "age factor" does not represent a single influence but rather a complex interaction of many elements. It was, therefore, felt that an analytic approach would be most suitable for bringing out the components. Accordingly the review is divided into three parts and each part is subdivided into several sections and sub sections. Part I depicts the variable outcomes of encounters between viruses and hosts of different ages under natural conditions. Part II illustrates : (a) the importan c e of extrinsic and intrinsic factors in the determination of the changes in susceptibility with maturation ; (b) the variable manifestations of these changes; and (c) the variability of the direction of these changes. Part III attempts a correlation between the changes in susceptibility and the alterations in certain constitutional factors in the course of development and maturation. The review concerns chiefly the changes in susceptibility that occur in the course of embryonal development, early postnatal life, and ad ult life. We could find very little information on changes in senescence. The following table contains the breakdown of all sections and subsections:
The comparative prophylactic effectiveness of oral treatment with ribavirin (1-beta-D-ribofuranosyl-1,2,4,triazole-3-carboxamide; virazole) and amantadine hydrochloride against artificially induced infection with influenza A virus was evaluated in 29 seronegative men who received ribavirin capsules (200 mg) three times daily, placebo capsules three times daily, or amantadine capsules (100 mg) twice daily. Medication was started two days before the inoculation of 2 X 10(4) 50% tissue culture infective doses of A University of Maryland/2/74 (H3N2) influenza virus and was continued for eight days after challege. Nine of the 10 subjects who received ribavirin, eight of the nine subjects who received placebo, and six of the 10 subjects who received amantadine developed influenzal illness. Significantly less virus was isolated from the amantadine-treated group than from the placebo-treated or the ribavirin-treated group. Antibody responses of the ribavirin-treated and placebo-treated groups were quite similar to each other; however, prophylactic treatment with amantadine significantly reduced titers of serum antibody and febrile responses. In a separate clinical trial involving challenge with A/Dunedin/73 (H3N2) influenza virus, ribavirin also failed to show prophylactic effectiveness.
We have reported that serum antibodies of the gar, Lepisosteus platyrhincus, a fresh water holostean fish, are restricted to the macroglobulin fraction (1). In studies to be reported we will present evidence that this species forms only one class of immunoglobulin, i.e., IgM (Bradshaw, C. M., Clem, L. W., and Sigel, M. M., to be published). In more recent work we have detected IgM antibody in mucus secretions of the gar. These findings are presented in the present paper.Materials and Methods. Animals. The collection, maintenance and bleeding of the gar, Lepisosteus platyrhincus, were as described previously ( 1 ) .Fish were immunized with 1 ml of sheep erythrocytes (ShE) prepared in 0.15 M phosphate buffered saline (PBS), pH 7.2, and standardized spectrophotometrically to 1 x 1 O9 cells/ml, administered intramuscularly into two sites on either side of the backbone.Mucus preparation. Mucus was collected by wiping seven fish with filter paper. 150 ml of Tris-HC1 buffer, 0.14 M NaCl, pH 7.4, was added and allowed to stand overnight a t 4'. The material was then centrifuged a t 1500 rpm for 20 min and the supernatant was concentrated by positive pressure dialysis (1 atm of pressure) at 4".Antibody assay. Antibodies were detected by agglutination of ShE or other erythrocytes using the microtiter assay system (Cooke Eng. Co., Alexandria, Va.). The standard diluent for all antibody assays was PBS. Erythrocytes were washed three times with PBS and standardized spectrophotometrically to 1 x 1@ cellsJm1 for titration. Serum or mucus samples were serially diluted in a
Interstitial tissue of the testis consists of Leydig cells, macrophages, lymphocytes, plasma cells, mast cells and fibroblasts. Previously we have reported that interleukin-1 (IL-1) inhibits Leydig cell androgen production. In the present study, the effect of IL-2 was investigated. Leydig cells (10(5) cells/ml) from adult Sprague-Dawley rats were cultured with or without IL-2 for 24 h. After medium changes, human CG (hCG), 8-bromo-cAMP, or forskolin was added with or without IL-2. Cultures were continued for an additional 24 h, and testosterone and cAMP levels were measured. IL-2 up to 100 U/ml had no effect on basal testosterone production. hCG-stimulated testosterone formation was inhibited in a dose-dependent manner by the addition of IL-2. IL-2 in a concentration of 100 U/ml decreased hCG-induced testosterone formation from 49.6 +/- 3.6 ng/ml (mean +/- SE) to 8.5 +/- 4.2 ng/ml. The hCG dose-response curve was shifted to the right by the addition of IL-2. Maximal testosterone production in response to hCG was reduced 40% in the presence of IL-2 (50 U/ml) without alteration of median effective dose (ED50). IL-2 also inhibited hCG-induced cAMP formation and 8-bromo cAMP- and forskolin-stimulated testosterone production. However, IL-2 did not alter the binding of [125I]hCG to purified Leydig cells. Furthermore, IL-2 significantly inhibited the conversion of 20-OH-cholesterol, 22-OH-cholesterol, pregnenolone, progesterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone to testosterone but did not alter the conversion of dehydroepiandrosterone and androstenedione to testosterone. Our results suggest that a T cell growth factor, IL-2, is a potent inhibitor of steroidogenesis. IL-2 may play a paracrine role in modulating Leydig cell function.
Previously, we have reported that interleukin-1 (IL-1) can modulate Leydig cell steroidogenesis. Recently, IL-1-like material has been shown to be present in the testis; however, the cellular source of this material remains unclear. In the present study we found that human recombinant IL-1 beta (1-100 ng/ml) caused dose-dependent increases in IL-1 alpha mRNA expression in Leydig cells. Similar to that reported in other tissues, IL-1 alpha mRNA from Leydig cells is mainly 2.2 kilobases. IL-1 alpha mRNA expression in Leydig cells was detectable as early as 2 h after the addition of IL-1 beta (10 ng/ml) and persisted for up to 24 h. Lipopolysaccharide also stimulated IL-1 alpha mRNA expression in these cells, but phorbol ester had no effect. Our results indicate that Leydig cells are a potential source of IL-1, which has both autocrine and paracrine effects.
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