Production of an Interleukin-1 Inhibitory Factor by Human Alveolar Macrophages from Normals and Allergic Asthmatic Patients

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Abstract
In order to study the possible role of alveolar macrophages (AMs) in the development of local immune responses, we compared interleukin-1 (IL-1) production by peripheral blood monocytes and AMs from 17 allergic asthmatics and 32 controls. When stimulated by lipopolysaccharide, alveolar macrophages and blood monocytes from controls released IL-1 (127 ± 74.6 and 178.8 ± 120 IL-1 units/ml, respectively) in the same amounts as AMs and blood monocytes from allergic asthmatics (148 ± 47.5 and 160.5 ± 78.3 IL-1 units/ml, respectively). After stimulation by anti-IgE or the specific allergen, asthmatic blood monocytes released IL-1-like activity (71.8 ± 46.4 and 45.4 ± 25.9 IL-1 units/ml, respectively). In contrast, asthmatic AM supernatants contained no detectable IL-1-like activity after stimulation by allergen or anti-IgE. The same pattern was observed with monocytes and AMs from controls after passive cell sensitization with 20% of IgE-rich serum. In a second step, the effect of supernatants of IgE-dependent stimulated AMs was tested on thymocyte proliferation induced by a purified IL-1, permitting the demonstration of an IL-1 inhibitory factor released by the AMs while these supernatants didn't modify the IL-2-dependent proliferation of a CTL-L line. The use of indomethacin and assessment of PGE2 levels in AM supernatants made it possible to discard the role of prostaglandins in this inhibitory effect. Moreover this activity, which is resistant to heat and trypsin treatment, has a molecular mass between 40 and 50 kD and did not correspond to serum proteases, alpha-1-antiproteinase, and arginase. Thus, our results demonstrate that contrary to some stimuli, like endotoxins which are able to induce IL-1 production, AMs after IgE-dependent stimulation deliver a negative signal for lymphocyte proliferation, suggesting an in situ limitation of the immune response.