In vivo administration of interleukin-6 in murine allogeneic bone marrow chimeras: early and delayed enhancement of hematopoiesis accompanied with split tolerance but not with graft-versus-host disease.
Interleukin-6 (IL-6) induced increased, leukocyte and platelet counts on around day 20 when it was administered into [BALB/c-->C3H/He] bone marrow chimeras from day 1 to day 12. Increased leukocyte counts and hemoglobin (Hb) levels were also observed at around day 60 and from day 41 to 80, respectively. On the other hand, hematopoietic recovery in [C3H/He-->C3H/He] bone marrow chimeras injected with IL-6 was different from that in [BALB/c-->C3H/He] bone marrow chimeras, showing no delayed and long-lasting increase in Hb levels but showing an early and transient increase in Hb levels and platelet counts. Sera from [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 showed predominant productions of IL-3 and/or IL-4. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that stem cell factor (SCF) mRNA expression was increased in bone marrow or spleen cells from [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 on day 36. Furthermore, we analyzed influence of IL-6 on graft-versus-host disease (GVHD) in [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6. Decreased survival days and body weights were not observed when compared with the control. Histopathological changes of the liver due to GVHD were also not obvious. However, alloreactive mixed lymphocyte reactions (MLRs) were readily detected although cytotoxic T cells were not generated. Since H-2 typing showed that donor-type chimerism was predominantly observed, it was suggested that split tolerance might be induced by IL-6 administration. Increased IL-2 levels were not detected in sera from [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 whereas IL-4 was detected in the same sera, indicating that type 2 helper T (TH2) cells appeared to be predominantly generated. These results suggest that IL-3/IL-4 and SCF appeared to synergistically support delayed effects on hematopoiesis in [BALB/c-->C3H/He] bone marrow chimeras injected with IL-6 although early effects appeared to be mediated mainly by IL-6 directly or indirectly. Furthermore, IL-6 could induce split tolerance in [BALB/c-->C3H/He] bone marrow chimeras via a preferable activation of TH2 type cells without inducing severe GVHD.
Imamura
M
M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hashino
S
S
Kobayashi
H
H
Tanaka
J
J
Imai
K
K
Han
M
M
Fujii
Y
Y
Kobayashi
M
M
Higa
T
T
Kasai
M
M
D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007378:Interleukins / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger