Heat stable interleukin-1 activity and activity inhibiting thymocyte proliferation in inflammatory polymorphonuclear...

The present study demonstrates the co-existence of heat stable interleukin-1 (IL-1) and IL-1-suppressing activity in murine inflammatory polymorphonuclear leukocytes (PMNs). When the IL-1 activity in casein-induced PMN lysate was examined by lymphocyte activating factor assay, it peaked at a concentration of 2.5 x 10(6) cells per ml, but this activity was reduced to nothing at higher concentrations, suggesting the co-existence of IL-1 and IL-1-suppressive factors in PMNs. Although IL-1 has been reported to be inactivated by heat treatment, approximately one-fourth of the IL-1 activity was restored after treatment at 100 degrees C for 10 min. In gel chromatography, the IL-1 activity of the PMN-soluble fraction was eluted in two broad peaks with apparent molecular sizes of 17-23 kDa and 23-43 kDa, respectively. Since the heat stable IL-1 activity was mainly eluted in fractions corresponding to the latter peak, and was neutralized by IL-1 receptor antagonist (IL-1ra) or anti-IL-1 alpha antiserum, the heat stable IL-1 is suggested to be precursor form IL-1 alpha. A high concentration of soluble fraction from PMN lysate, in contrast, completely suppressed the activity of recombinant IL-1 alpha or beta, and the suppressive activity was heat labile. Since thymocyte mitogenesis by 5 micrograms/ml of concanavalin A (Con A) with or without IL-2 was also completely suppressed, the suppressive factor(s) may not be IL-1ra or transforming growth factor beta which were reported to be present in PMNs.