Increased Bone Marrow Production of Granulocytes and Mononuclear Phagocytes Induced by Mycobacterial Adjuvants: Improved Recovery of Leukopoiesis in Mice After Cyclophosphamide Treatment

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Abstract
The effects of complete Freund adjuvant (CFA) or Mycobacterium bovis BCG on leukopoiesis and on leukopoietic recovery from cyclophosphamide [CP] treatment in mice was studied. CFA injected s.c. or i.p. resulted in increased blood granulocyte and monocyte counts, increased numbers of bone marrow granulocyte and mononuclear phagocyte progenitors, and increased hematopoietic colony-stimulating factor in the serum. The quantitative cellular response within 24 h to an induced sterile i.p. inflammation (thioglycolate) was augmented by s.c. CFA. In mice given CFA s.c., blood granulocyte counts, as well as the peritoneal granulocyte and macrophage response to i.p. thioglycolate, recovered more quickly than did those of the controls after a 250-mg/kg dose of CP. CFA-treated mice consistently maintained blood granulocyte and monocyte counts 1.3- to 4-fold higher than those of the controls for 2 wk while receiving 75 mg of CP/kg every other day. Mice pretreated with CFA i.p. had higher numbers of bone marrow colony-forming units in culture and higher levels of serum colony-stimulating factor after 250-mg/kg injections of CP. Similarly, BCG resulted in increased bone marrow colony-forming units in culture, increased serum colony-stimulati factor and a faster return of the peritoneal inflammatory response after CP injection. Mycobacterial adjuvants accelerate recovery of leukopoietic functions after CP treatment. There may be a mechanism whereby such adjuvants afford nonspecific protection against infection in immunosuppressed mice.