The injection of alpha-MSH or of one of its analogues ([Nle4-D.Phe7] alpha-MSH4-10) reduced, in vivo, the release of two cytokines (IL-1 alpha and TNF alpha) involved in inflammation. The inflammatory state was induced in BALB/c mice by intraperitoneal injection of a sublethal dose of lipopolysaccharides (LPS). The assay of these cytokines by ELISA showed a reduction of 20% with alpha-MSH and between 30 and 60% with the alpha-MSH analogue. The alpha-MSH or the analogue was administered in one of two ways: intravenously or subcutaneously. The most efficient method seemed to be the subcutaneous one because it improved the activity 10,000 times more than the intravenous method. Moreover, the analogue induced a regression of mortality in the animals treated by the intravenous method. Our results show that alpha-MSH and one of its analogues inhibit IL-1 alpha and TNF alpha, and can be used as anti-inflammatory molecules.

No abstract

Sir, Dr. Fukunaga and colleagues have observed that liposome-entrapped calcitonin administered orally to fasting male rats resulted in a light hypocalcemia when the phospholipids layers contained stearylamine (Fukunaga, Miller and Deftos 1991). However, even with this improvement, the hypocalcemia measured was much lighter than when the hormone was injected (Dupuy, Peuchant, Vitiello, Jensen, Baghdiantz and Blanquet 1983; Dupuy 1983). The advantage in oral administration of this peptide led us to examine why it was inefficient.