Interleukin-12 corrects severe anemia during blood-stage Plasmodium chabaudi AS in susceptible A/J mice.
The in vivo role of interleukin (IL)-12 in correcting anemia and the underlying defect in erythropoiesis in Plasmodium chabaudi AS-susceptible A/J mice was examined. Six daily intraperitoneal injections of 0.1 microg IL-12 in A/J mice, beginning on the day of infection, rapidly and significantly enhanced bone marrow and splenic erythropoiesis as demonstrated by marked increases in early and late committed erythroid progenitors, the erythroid burst (BFU-E) and colony-forming units (CFU-E), respectively, compared with control mice. The most dramatic effect of IL-12 treatment was a sevenfold increase in the number of splenic CFU-E on day 7 postinfection, compared with untreated, infected A/J mice. Treatment with IL-12 also caused significant increases in hematocrit levels, erythrocyte counts, percentage of reticulocytes, spleen cellularity, and frequencies of BFU-E and CFU-E in the bone marrow and spleen of A/J mice during infection. The frequency of BFU-E in the peripheral blood of these mice was also significantly increased, suggesting enhanced mobilization of precursor cells to the spleen as well as increased production of erythroid precursors in this organ. Consistent with previous observations using higher doses, 0.1 microg IL-12 administered daily for 6 days to normal A/J mice significantly decreased bone marrow erythropoiesis and significantly increased splenic erythropoiesis. However, the influence of IL-12 on erythropoiesis was much more pronounced during ongoing malaria infection. These results suggest a role for IL-12 during blood-stage malaria in not only enhancing the development of protective immunity but also in alleviating malaria-induced anemia by increasing the number of erythroid precursors and enhancing the expansion of committed erythroid progenitors.
Mohan
K
K
Centre for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada.
Stevenson
M M
MM
D000740:Anemia / Q000188:drug therapy*; D000818:Animals; D004198:Disease Susceptibility; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use*; D008288:Malaria / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D016788:Plasmodium chabaudi; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D011994:Recombinant Proteins; D018664:Interleukin-12