Suppression of graft-versus-host reaction by preincubation of the graft with an antitumor protein, neocarzinostatin.
The immunosuppressive activity of neocarzinostatin, an antitumor antibiotic with a high molecular weight, was demonstrated, as measured by the local and systemic graft-versus-host reaction in rats. The preincubation of parental strain lymphocytes with doses more than 1 micrograms/ml of neocarzinostatin for at least 10 min at 37 degrees C resulted in the marked suppression of the popliteal lymph node enlargement, when injected subcutaneously into the hind footpads of F1 hybrid rats. The suppressive effect was temperature-dependent and irreversible, because the neocarzinostatin (1 microgram/ml) pretreatment of parental lymphocytes at 4 degrees C was not effective in the suppressive activity, and the reincubation of cells after the removal of the drug from the culture did not result in demonstrable changes in the degree of suppression. The neocarzinostatin pretreatment does not result in visible changes in the oxygen consumption rate and viability of cells in vitro or in the distribution pattern within a regional lymph node, indicating that treated cells may retain the same viability and migration capacity in vivo as do untreated cells. Furthermore, the drug pretreatment resulted in the complete prevention of runting syndrome, when treated parental lymphocytes were injected intravenously into F1 hybrid rats.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006086:Graft vs Host Disease / Q000517:prevention & control; D006087:Graft vs Host Reaction / Q000187:drug effects*; D007166:Immunosuppressive Agents; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology; D013696:Temperature; D009353:Zinostatin / Q000494:pharmacology* / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D009353:Zinostatin