The treatment of induced immune deficiency with interleukin-2.
In vivo generation of alloreactive cytotoxic T lymphocytes (CTL) was found to be inhibited by treatment of mice with either cyclophosphamide or the glucocorticoid, hydrocortisone acetate. The effects of these immunosuppressive agents could be overcome, however, by the in vivo administration of IL-2 from both murine and human sources. Both human IL-2 derived by recombinant DNA techniques as well as the natural protein from mouse and man all reverse the unresponsive state. A single injection of IL-2 was sufficient to reverse the effect of cyclophosphamide treatment, while additional injections with as little as 8 micrograms of protein ablated the steroid-induced suppression. Furthermore, the responder cells generated in vivo following IL-2 therapy were shown to be antigen specific in terms of their lytic capacity. Thus, IL-2 therapy appears to restore the in vivo responsiveness of immunosuppressed recipients to allogeneic tumor cell challenge. These data demonstrate the importance of IL-2 as an immunoregulatory molecule in vivo and suggest its future use as a potent therapeutic.
Conlon
P J
PJ
Washkewicz
T L
TL
Mochizuki
D Y
DY
Urdal
D L
DL
Gillis
S
S
Henney
C S
CS
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000939:Epitopes; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced / Q000188:drug therapy*; D007376:Interleukin-2 / Q000627:therapeutic use*; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D000939:Epitopes; D007376:Interleukin-2; D011994:Recombinant Proteins; D003520:Cyclophosphamide; D006854:Hydrocortisone