Evidence for Biochemically Distinct Forms o f IL - 1 BY PATRICIA CAMERON

The term interleukin 1 (IL-1) encompasses macrophage-derived polypeptide factors in man, mouse, and other animals, which stimulate murine thymocyte proliferation (1-3), and in addition activate various target cells involved in chronic inflammation (4-10). The IL-1 produced by the murine macrophage line, P388D1, has a low isoelectric point (pI) and exhibits micro-charge heterogeneity in the range of 4.9-5.2 (11). P388Dl-derived IL-1 has been purified (1 1), and a complementary DNA (cDNA) 1 coding for the precursor form of this molecule has been recently cloned (12). The nucleic acid sequence of this cDNA was validated by sequencing peptides of P388Dl-derived I L-1 protein (12). The study of human IL-1 has lagged behind that of murine IL-1 largely because of the unavailability of a tumor line capable of making large amounts of IL-1. In addition, human IL-1 appears more complex than murine IL-1, in that there are several major charged species (4, 5, 13). Like murine IL-1, two of these species have low pI, 5. ! and 5.3. Porcine IL-1, also known as catabolin, also has a pI in this range (14). In contrast to the mouse and pig, there is, in man, a third type, with a pI of 6.0, and a fourth, dominant species, with a pI of 6.8 (4, 5, 13). The pI 6.8 species has been purified (15), while several of the low-pI human types have been purified by others (16). The biochemical relationships among these various charged species is not known, though their similar bioactivities on fibroblasts (4, 5) and other target cells (17) have suggested to some that they might share similar core structures. A cDNA putatively coding for a human IL-1 molecule has recently been reported (18). The translation product derived from this cDNA was (a) active on D10.G4.1 T cells, a cell line responsive to partially purified preparations of murine IL-1 (19), and (b) precipitated by a polyspecific antiserum containing antibodies against several charged species of human IL-1 (20), and several other macrophage-derived products (18). However, the translation product was not shown to be active in the murine thymocyte proliferation assay, the standard assay for all IL-1 molecules. Furthermore, no amino acid sequence analysis of