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The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, showed in vivo immunomodulatory capacities qualitatively and quantitatively comparable to those of the mature human IL-1 beta protein. In fact, both IL-1 beta and the 163-171 fragment stimulated the immune response of normal mice and restored immune reactivities of immunocompromised animals. In addition, the synthetic IL-1 peptide was as efficient as the entire protein in inducing tumor rejection and radioprotection. On the other hand, the 163-171 fragment did not cause any of several inflammation-associated metabolic changes inducible by the whole IL-1 beta molecule in vivo: hypoferremia, hypoglycemia, hyperinsulinemia, increase in circulating corticosterone, SAA and fibrinogen, decrease in hepatic drug-metabolizing enzymes. Furthermore, at variance with IL-1 beta, the 163-171 peptide did not show the toxic effects causing shock and death in adrenalectomized mice. Thus, these results confirm our previous in vitro observations that functional domains are identifiable within the multipotent cytokine IL-1 beta, and demonstrate the biological relevance of this finding in a variety of in vivo systems. The identification of a selectively active fragment of a cytokine may thus represent a significant step towards a better directed and more rational immunotherapeutic approach.

The expression of a molecule recognized by anti-galactosyl ceramide antibodies (MAb) O1 on the surface membrane of human spermatozoa was investigated by biochemical and immunochemical methods. Indirect immunofluorescence shows that this molecule is preferentially localized on the middle piece of the sperm tail. Immuno-thin-layer chromatography has identified it as a glycolipid related but not identical to galactosylceramide. Consistent with a structure similar to galactosylceramide, the sperm glycolipid is capable of binding gp120. An improved ELISA has been utilized to demonstrate the specificity of binding of the antibodies and gp120 to the isolated lipid fraction. Identity of the binding site of the two ligands to the glycolipid is suggested by competition assays. On the basis of preliminary biochemical analysis this glycolipid was tentatively classified as a galactosylalkylacylglycerolipid (GalAAG), the nonsulfated form of the seminolipid, a glycolipid known to be present in the testis and germ cells of mammals. These data indicate that human sperm express a glycolipid similar in structure to the receptor for HIV described on the CD4- neural and colonic epithelial cell lines, and moreover suggest that this glycolipid could also function as HIV receptor and possibly be implicated in its transmission.

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