Cytokines and evolution: in vitro effects of IL-1 alpha, IL-1 beta, TNF-alpha and TNF-beta on an ancestral type of stress response.

Invertebrate hemocytes are immune-neuroendocrine cells which contain a variety of cytokines [Ottaviani et al. (1993) Biochem. Biophys. Res. Commun. 195, 984-988] and release biogenic amines when added to corticotropin-releasing factor (CRF), a phenomenon we have described as an evolutionary proto-type stress response [Ottaviani et al. (1991) Proc. R. Soc. Lond. B 245, 215-218]. Here we show in two molluscs, Planorbarius corneus and Viviparus ater, that this response is significantly reduced when hemocytes are pre-incubated with IL-1 alpha, IL-1 beta, TNF-alpha and TNF-beta before the addition of CRF. These results confirm and extend the hypothesis that a deep evolutionary relationship exists between cytokines and stress response. Moreover, these data offer an evolutionary basis for understanding the promiscuity of cytokine receptors.