The urine of febrile patients has been found to contain high concentrations of an inhibitor of interleukin 1 (IL-1)-induced thymocyte proliferation. The inhibitor is specific for IL-1 and does not block the effects of interleukin 2 (IL-2) or phytohemagglutin (PHA) on thymocytes, and it is not nonspecifically toxic for these cells. IL-1 inhibitor can be found in the urine of normal individuals and afebrile patients, but is present in increased concentrations in the urine of patients with fever of diverse etiologies. Preliminary physicochemical characterization indicates that the inhibitor is a 20-40-kdalton protein.

Pulmonary eosinophilic granuloma is a disorder caused by localized collections of proliferating histiocytes in the lung. Little is known about its etiology except that the majority (58 to 97%) of patients are current or ex-smokers, making the potential etiologic role of tobacco products an important area for research. Tobacco glycoprotein (TGP) is a potent immunostimulator that has been isolated from cigarette smoke. TGP-specific lymphocyte proliferation, and cytokine production in vitro, were measured in three patients with pulmonary eosinophilic granuloma in remission and in three closely matched normal subjects with similar smoking histories. One patient with eosinophilic granuloma of bone and a matched control subject were also studied. Peripheral blood mononuclear cells were cultured with TGP, the recall antigen streptokinase (SK), and the mitogen concanavalin A (Con A). All three of the patients with pulmonary eosinophilic granuloma exhibited significant decreases in lymphocyte stimulation to TGP, despite normal responses to SK and Con A. In contrast, the response of the patient with eosinophilic granuloma of bone was higher than her matched control. The mean responses of the patients with pulmonary eosinophilic granuloma to TGP was significantly lower than the mean of nondiseased smokers or of normal nonsmokers. Twenty-four-hour culture supernatants were collected and assayed for cytokine levels (IL-1, IL-2, and IL-6). TGP-stimulated IL-2 production was significantly lower in the patients with pulmonary eosinophilic granuloma than in the normal subjects, confirming the reduced T-cell proliferative response.(ABSTRACT TRUNCATED AT 250 WORDS)

Our laboratory previously noted an increase in thymocyte mitogenic activity in the urine of many elderly patients. The present study was performed to verify this finding and to determine if this activity was actually due to an increase in interleukin-1 (IL-1). IL-1 levels were measured in the urine of 33 healthy, ambulatory, elderly subjects (ages 83-95 years), using both a murine thymocyte bioassay, measuring activation by the incorporation of tritiated thymidine and an MTT dye reduction assay. There was a significant increase in urine IL-1 in 85% of elderly individuals. In the MTT dye reduction assay, mean elderly urine IL-1 levels were 0.88 U/ml, in comparison with a young control group (ages 23-37 years) in which urine IL-1 levels were very low (mean IL-1 ≤0.05 U/ml). Urine levels of IL-1β were also measured by using a sensitive immunoassay (ELISA) and were found to be significantly increased in the elderly (mean = 57.4 pg/ml), compared to the young (mean = 2.5 pg/ml). In contrast, IL-2 levels in urine were very low, with no difference between the young and the elderly. Mean urine protein and creatinine levels did not differ significantly between young and old, and did not account for the increase in urine IL-1 levels. Although its immunologic significance is not yet understood, this striking increase in IL-1 is an unusual and interesting finding that merits further investigation.

IL-4 production significantly increased at low concentrations of CH(3)Hg (0.5 uM, p < 0.01), while gamma-IFN production was suppressed starting at CH(3)Hg 2 uM (p = 0.004). Inorganic mercury (HgCl(2)) increased IL-4 only at concentrations 10-20 times higher than CH(3)Hg. These findings suggest a mechanism by which mercury could trigger or potentiate TH2 cytokine production in humans.

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