Therapeutic and prophylactic agents and methods of using the same

Abstract

A phospholipase A.sub.2 inhibitor protein designated "Phospholipase Inhibitor from Python" (PIP)--formerly designated "Python Antitoxic Factor" (PAF)--is given by SEQ ID NO:2. The partial amino acid sequence for PIP was initially determined from the native protein purified from the blood serum of a non-venomous snake, Python reticulatus. The complete PIP polynucleotide sequence was obtained from a cDNA clone encoding PIP, given by SEQ ID NO:1, along with the full amino acid sequence deduced from it. Also disclosed is a recombinant protein PIP, which shows strong lethal toxin neutralizing activity similar to the native PIP, and has potent anti-inflammatory activity. Both the native and the functionally equivalent recombinant PIP are useful for the prevention or treatment of conditions such as snakebites, insect stings, and inflammatory diseases. Also, phospholipase A.sub.2 (PLA.sub.2) inhibitory polypeptides designated P-0029, P-0009, and P-0006, the sequences of which are given as SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, respectively, are disclosed. Those polypeptides, and their synthetic chemical analogues and polypeptide variants that inhibit PLA.sub.2 activity and alleviate inflammation, may also be used in the diagnosis, study, prevention, and treatment of PLA.sub.2-related human inflammatory diseases.