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Insulin-like growth factor I (IGF-I), a 70 aminoacid-long polypeptide with several metabolic and proliferative actions, is expressed in the rat brain during development and after acute injury [1–3]. The neuroprotective effect of IGF-I has been recently demonstrated in vitro using differentiated PC 12 cells undergoing apoptosis [4], cerebellar granules cultured in the presence of low K+ concentrations [5], and primary rat hippocampal neurons [6]. Moreover, there is a growing body of evidence showing that IGF-I injected intracerebroventricularly (icv) is neuroprotective in several experimental models of acute neuronal injury [7–8]. This suggests a possible therapeutic use for this trophic factor in peripheral or central nerve injuries. Some of the biological effects of IGF-I are probably mediated by des(1–3)IGF-I, an IGF-I derivative lacking the N-terminal tripeptide glycine-proline-glutamate (GPE). Des(1–3)IGF-I has been detected in the human brain (among other tissues) and is generally more potent than IGF-I in several in vitro assays [9–12]. The recent observation of Guan et al. that des(l-3)IGF-I is less effective then recombinant human IGF-I (rhIGF-I) as a neuronal rescue agent suggests that the central effects of this growth factor might be partially mediated by the N-terminal tripeptide GPE [13]. GPE (10-5 M) exhibits in vitro mitogenic properties on glial cells [14], modifies gonadotropin releasing hormone in response to N-methyl-d-aspartate (NMDA) receptor agonists [15–16] and potentiates K+-induced dopamine release from rat striatal slices [17]. All these effects probably involve NMDA receptor-mediated events, since they can be reverted by specific NMDA receptor antagonists.

Interleukin 2 (IL-2) is a cytokine produced by activated T cells that plays a crucial role in the immune response and exerts multiple functions in different tissues including the nervous system. The present study was carried out to investigate the effect of recombinant human IL-2 (rhIL-2) on the survival of differnet glial cells type and of cortical neurons in culture. The results demonstrate that rhIL-2 is selectively cytotoxic to oligodendrocytes only if preincubated in aqueous solution (1200 U/ml) for at least two days before being added to the culture. Other glial and neuronal cells were unaffected. The cytotoxic effect was temperature- and concentration-dependent occurring only when rhIL-2 was reincubated at 37 degrees C and was dose-dependently neutralized by antibodies raised against IL-2 indicating that an immunoreactive IL-2 like compound is the active principle. Polyacrilamide gel electrophoresis under native (PAGE) and denaturing (SDS-PAGE) conditions and gel filtration analysis of the rhIL-2 incubated solution suggest that rhIL-2 is cytotoxic to oligodendrocytes only after association into soluble high weight molecular aggregates.