Recombinant human IL-2 is cytotoxic to oligodendrocytes after in vitro self aggregation.
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.
Curatolo
L
L
Pharmacia & Upjohn, CNS and Oncology Research, Nerviano (Milano), Italy.
Valsasina
B
B
Caccia
C
C
Raimondi
G L
GL
Orsini
G
G
Bianchetti
A
A
D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000633:toxicity*; D009836:Oligodendroglia / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology / Q000633:toxicity
D007376:Interleukin-2; D011994:Recombinant Proteins