ABSTRACT
The bone marrow cytokine (Bio-Immuno Modulator, BIM or BM-Fr1) has been suggested to correct immunoincompetence by modulating brain Na(+)-K(+)-ATPase. The brain region affected and mechanism of action of BM-Fr1 are unknown, however. Here we report that immunization of immunocompetent rats indirectly inhibited Na(+)-K(+)-ATPase activity (59%) in the left cerebral lobe (LC) and irrespective of BM-Fr1 treatment, stimulation of the enzyme was observed in the LC at the peak of immune response. BM-Fr1 treatment, which corrected immunoincompetence in malnourished rats, also modulated a different LC Na(+)-K(+)-ATPase profile to that seen in immunocompetent animals. Immunogen and BM-Fr1 seem to exert their influence in brain via a cytosolic inhibitor protein of Na(+)-K(+)-ATPase. Thus we suggest that (1) BM-Fr1 plays an important role in immune homeostatasis by modulating Na(+)-K(+)-ATPase activity of LC and (2) Na(+)-K(+)-ATPase is not the receptor for either immunogen or BM-Fr1.
Subject(s)
Brain/enzymology , Cytokines/pharmacology , Immunization , Sodium-Potassium-Exchanging ATPase/metabolism , Adjuvants, Immunologic/pharmacology , Animals , Female , Homeostasis/immunology , Immunocompetence , Immunosuppression Therapy , Male , Nutritional Status , Rats , Sodium-Potassium-Exchanging ATPase/drug effectsABSTRACT
After sheep erythrocyte (SRBC) immunization in balanced-diet-fed (BDF) rats, the brain microsomal ATPase activity for the first 48 h was suppressed compared with preimmunization level, then stimulated at the peak of the immune response. In contrast, rats malnourished by deprivation of vitamin B complex and ascorbic acid and with significantly lower pre- and postimmunization enzyme activity than the BDF rats, had stimulated enzyme activity only on immunization, and their immune response was found to be suppressed. A bone marrow-derived bioimmunomodulator (BIM) revived the immunocompetence of the malnourished immunized animals, and brain ATPase activity in these animals after BIM injection followed a pattern similar to that of the immunized BDF rats. We suggest that, after SRBC immunization under the influence of BIM, suppression followed by stimulation of the brain microsomal ATPase might be related to immune response.
Subject(s)
Adenosine Triphosphatases/metabolism , Adjuvants, Immunologic/metabolism , Bone Marrow/immunology , Brain/enzymology , Brain/immunology , Nutrition Disorders/enzymology , Nutrition Disorders/immunology , Animals , Animals, Newborn , Calcium-Transporting ATPases/metabolism , Cytokines/metabolism , Erythrocytes/immunology , Female , Immunization , Immunocompetence , Male , Rats , Rats, Inbred Strains , Sheep , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
Vaccine failure attributable to immunodeficiency is common in stressed individuals. During vitamin-B complex and ascorbic acid malnutrition in experimental animals, vaccine failure is accounted for by the atrophy of the immunocompetent organs. In an attempt to improve immunocompetence, a bioimmunomodulator obtained from the supernatant fluid from cultured normal bone-marrow cells was injected following immunization into young animals receiving a diet deficient in vitamins B and C. This treatment improved the immunosurveillence of mice and rats approximately 3 to 4 fold. Peculiarly, this factor failed to evoke immunostimulation in normal immunized animals, probably because of a suppressing mechanism.
