Cytokine involvement in immunomodulatory activity affected by Candida albicans mannan.
Candida albicans mannoprotein (MAN) administered intravenously to mice stimulates the production of splenic CD8+ effector cells which downregulate delayed hypersensitivity (DH) in immunized mice. Cytokine involvement in the induction and/or elicitation of downregulation was studied by (i) examining murine splenocytes qualitatively for mRNA for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, and gamma interferon (IFN-gamma), (ii) quantitating splenocyte mRNA for IL-12p40 by quantitative-competitive reverse transcriptase-mediated PCR, and (iii) measuring serum levels of IL-12p40 and IL-12p70 by capture enzyme-linked immunosorbent assay, each performed at selected intervals over 96 h after giving MAN. Further, the effect of in vivo administration of anti-IL-4 on the induction and elicitation of MAN-specific DH in MAN-treated mice was measured. Expression of IL-12p40 mRNA in the spleen was reduced to near 0 during the first 24 h but rebounded thereafter. Transcripts for IL-10 were present throughout the 96-h period, whereas those for IL-4 and IFN-gamma were either weak or undetectable prior to 24 to 48 h. In vivo administration of anti-IL-4 partially abrogated the downregulatory effect of MAN only when given at the time of MAN administration. Serum levels of IL-12p40, but not IL-12p70, were increased by 24 h and maximal at 48 h. The antagonistic effect of IL-12p40 could contribute to the mechanism(s) for downregulation of DH. Moreover, IL-10, IL-4, and/or IFN-gamma, interacting with MAN-activated cells in the absence of biologically active IL-12, may induce the production of CD8+ downregulatory effector cells. Partial abrogation of downregulatory activity in animals treated with anti-IL-4 at the time of induction of such activity lends support to this hypothesis.
Wang
Y
Y
Department of Microbiology and Immunology, Tulane University Medical School, New Orleans, Louisiana 70112-2699, USA.
Li
S P
SP
Moser
S A
SA
Bost
K L
KL
Domer
J E
JE
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D007114:Immunization; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008297:Male; D008351:Mannans / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000032:analysis
D016207:Cytokines; D008351:Mannans; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4