Biochemical heterogeneity of human interleukin-1.

Human interleukin 1 (IL-1), a mediator of several host defense responses, is usually considered to have a molecular weight of 15,000 daltons and an isoelectric point near neutrality. However, during purification, significant IL-1-like activity is also found with apparent molecular weights of greater than 80,000, 50,000, and 35,000 daltons. The active species with the highest apparent molecular weight (greater than 80 kilodaltons) is not a strong comitogen for thymocytes but exhibits relatively strong direct mitogenic activity. By affinity By affinity chromatography, it was shown that the direct mitogen is probably a contaminant distinct from the IL-1. Significant IL-1 activity is also recovered at approximately 50,000 daltons, but upon rechromatography it dissociates, suggesting that it is an aggregate. In contrast, the species eluting at 35,000 daltons and 15,000 daltons are stable upon rechromatography even in 6 M urea. Upon isoelectric focusing, the 15,000 and the 35,000 dalton species show similar patterns, with a prominent peak of IL-1 activity near neutrality and multiple peaks in the range of pI 4.5-5.8. Therefore, it appears that human monocytes secrete at least four biochemically distinct and noninterconvertible proteins, all of which stimulate the proliferation of murine thymocytes in the presence of PHA. Although the IL-1 preparations described above were prepared by pooling IL-1-rich supernatants from 12 donors, the heterogeneity is not due to genetic diversity. A similar set of four molecules with IL-1 activity was derived from the leukocytes of a single patient with chronic myelomonocytic leukemia and from a single human placenta.