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Interleukin (IL)-1 is a key cytokine in inflammatory reactions. To clarify the mechanism of inflammation in the pleural cavity, we investigated the contribution of IL-1 and its antagonism to inflammatory processes in the pleural cavity. Interleukin-1 receptor antagonist (IL-1Ra) levels as well as IL-1 beta and interferon-gamma (IFN-gamma) levels were measured by enzyme immunoassay in pleural effusions from 70 patients. Pleural macrophages were also examined as possible sources of these cytokines in 10 patients. IL-1Ra was detectable in 28 patients (40%) out of 70 patients with pleural effusions. Patients with tuberculosis had significantly higher IL-1Ra as well as IFN-gamma levels in pleural effusion than patients with lung cancer. Transudative pleural effusions had low or undetectable IL-IRa levels. On the other hand, IL-1 beta levels were low, except in cases of parapneumonic pleural effusion. Spontaneous production of IL-1Ra pleural macrophages was observed in six patients, and IL-4 significantly augmented its production. Although spontaneous production of IL-1 beta was observed in only two patients, pleural macrophages produced significant amounts of IL-1 beta in response to lipopolysaccharide in all 10 patients examined. These results suggest that interleukin-1 receptor antagonist regulates various reactions by interleukin-1 in pleural effusion, and that pleural macrophages may act in situ as a source of interleukin-1 receptor antagonist.

Interleukin-4 (IL-4) has previously been found to downregulate interleukin-1 (IL-1) production, but to upregulate the production of IL-1 receptor antagonist (IL-1ra) in human monocytes stimulated with lipopolysaccharide (LPS). In the present study we wanted to determine whether the production of IL-1ra in human monocytes and alveolar macrophages (AMs) is regulated differently at the protein and messenger ribonucleic acid (mRNA) levels by IL-4 and interferon-gamma (IFN-gamma). AMs and monocytes obtained from healthy donors by bronchoalveolar lavage and centrifugal elutriation were stimulated with LPS in the presence or absence of IL-4 or IFN-gamma, and the expression of mRNA for IL-1 and IL-1ra was measured by Northern blot analysis. The production of IL-1 and IL-1ra was quantitated by enzyme immunoassays (EIAs). Spontaneous IL-1ra production was seen in AMs after incubation for 4 h in medium alone, but not in blood monocytes, at both the protein and mRNA levels. The spontaneous expression of the IL-1ra gene in AMs was augmented by incubation with IL-4. Interleukin-1 beta (IL-1 beta) production by LPS-stimulated AMs and monocytes was upregulated by IFN-gamma, but downregulated by IL-4. Interestingly, when stimulated with LPS, IFN-gamma inhibited IL-1ra production by monocytes, but up-regulated its production in human AMs at the protein and mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)