The paradoxical effects of somatostatin on the bioactivity and production of cytotoxins derived from human peripheral blood mononuclear cells

Abstract

Summary Somatostatin (SMS), a naturally occurring peptide is known to inhibit the production of certain protein molecules and to diminish the ability of peripheral blood mononuclear cells to proliferate. We tested the effects of three forms of SMS on the bioactivity of both lymphotoxin (LT) and tumour necrosis factor (TNF). We also tested the effects of these agents on production of cytotoxins by peripheral blood mononuclear cells. We found the 28 amino acid form of SMS significantly enhanced the bioactivity of both LT and TNF (10-9 M concentration) when tested in mouse L cells. The 14 amino acid form of SMS enhanced LT (10-9 M concentration) activity but not TNF activity. The first 14 amino acid form of SMS-28 (amino terminal) did not affect bioactivity of the cytotoxin. In contrast, the naturally occurring 14 amino acid form of SMS (10-8 M concentration) significantly diminished production of cytotoxin by human peripheral blood mononuclear cells. Cytotoxin produced by the latter was shown to be a combination of both LT and TNF.

Somatostatin and the immune and haematopoetic system; a review

“…The lymphotoxin (LT) and tumour necrosis factor (TNF)-induced destruction of mitomycin C treated murine L929 cells was enhanced by SS-14 and especially by SS-28 [54]. The observed cytotoxic effects in these experiments significantly increased over a narrow concentration range of SS.…”

“…SS and SS-analogues inhibit the secretion of hormones produced by normal endocrine cells as well as by neuro-endocrine tumours. Both LT and T N F release by perpheral mononuclear cells was significantly decreased by 10-100 nM SS [54]. In another study it was shown that SS and octreotide inhibit the secretion of INF-gamma but not INF-alfa by mononuclear cells at concentrations higher than 1 uM [55].…”

“…Apart from the influence of SS on cellular cytotoxicity, the influence of SS on the production of cytotoxic cytokines was also studied [54]. The lymphotoxin (LT) and tumour necrosis factor (TNF)-induced destruction of mitomycin C treated murine L929 cells was enhanced by SS-14 and especially by SS-28 [54].…”

“…The observed cytotoxic effects in these experiments significantly increased over a narrow concentration range of SS. The authors hypothesized that SS promotes cell injury by inhibiting the repair mechanism of the affected cells [54].…”

The effect of low dose octreotide administration on renal function and on gene expression of IGF-I axis components in experimental diabetes mellitus

“…In certain circumstances, the effect of somatostatin on the bioactivity and production of cytotoxins, especially TNF, was described to be paradoxical, i.e. enhancement of TNF activity by a lower concentration and suppressed activity in the presence of a higher concentration (Yousefi et al 1991). Since TNF induces insulin resistance (Bazzoni & Beutler 1996), its modulation by various doses of somatostatin or analogs may lead to an aggravation or attenuation of a pre-existing diabetic state.…”