Effects of bone marrow transplantation and polyinosinic-polycytidylic acid (poly I:C) on the rescue of animals from busulfan-induced NK suppression.
Repeated injections of busulfan (Bu) in CAF1 mice caused a long-lasting (greater than 16 weeks) decrease in their natural killer (NK) cell activity and impaired their resistance to transplantable lymphoma. Bu-treated mice had fewer spleen cells capable of binding to NK-sensitive YAC-1 target cells and reduced lymphokine-activated killer (LAK) cell activity as compared to normal age-matched controls. In contrast, interleukin 1 (IL-1) and interleukin 2 (IL-2) production were normal. Transplantation of normal bone marrow cells into Bu-treated mice resulted in an elevation of IL-2 production as well as in complete restoration of NK activity, target cell binding, and partial restoration of LAK activity. Resistance to transplantable lymphoma was equal to that of age-matched control mice. Polyinosinic-polycytidylic acid (Poly I:C) treatment resulted in immunomodulation in both control and Bu-pretreated mice. Twenty-four hours after Poly I:C injection, control and Bu-treated mice had higher levels of NK activity than did normal age-matched control mice, but the NK activity of Poly I:C/Bu-treated mice remained significantly lower than that of Poly I:C/control mice. The super-normal levels of NK activity in control and Bu-treated mice following Poly I:C administration were attributable, in part, to endogenous LAK activity. The generation of splenic LAK cells in vitro and target binding cells, which were reduced in Bu-pretreated mice, normalized following treatment with Poly I:C. Poly I:C treatment caused an increase in both IL-1 and IL-2 production in control and Bu-pretreated mice and in the ability of the treated mice to reject transplanted lymphoma cells. These results suggest that repeated injections of Bu decrease NK and LAK activity, but do not eliminate NK and LAK precursor cells. Thus, treatment with agents that increase IL-2 and/or interferon production can activate these cells to become effective killers and counter the long-lasting immunosuppressive effects of chemotherapy.[1]References
- Effects of bone marrow transplantation and polyinosinic-polycytidylic acid (poly I:C) on the rescue of animals from busulfan-induced NK suppression. Bhoopalam, N., Fried, W., Benson, D., Barone-Verales, J., Price, K. Exp. Hematol. (1989) [Pubmed]
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