Impairment of cytokine production in mice fed a vitamin D3-deficient diet.
C57Bl/6 female mice fed a Vitamin D (VIT-D)-deficient diet had serum levels of 25-hydroxyvitamin D decreasing with the time of diet exposure (3 and 8 weeks). Cytokine production (IL-6, TNF and IL-1) by peritoneal macrophages cultured in vitro with a standard stimulus, LPS, evaluated in the supernatants as biological activity, was significantly reduced in VIT-D-deficient animals. The defect in monokine production was partial and was evident at suboptimal LPS concentrations and incubation times. I-A antigen expression, induced in macrophages by in vitro exposure to IFN-gamma, was not modified in VIT-D-deficient mice, but IFN-gamma-inducible macrophage cytotoxicity to tumour target cells was significantly decreased in VIT-D-deficient animals. Moreover, basal and Poly I:C-induced NK activity was not modified by VIT-D deficiency. Thus, macrophage functions, such as cytokine production and tumour cytotoxicity induction, are down-modulated in vitro by VIT-D deprivation. To give more support to the relevance of VIT-D availability for cytokine production, TNF and IL-6 have been evaluated in the sera of control and VIT-D-deficient mice given LPS as a model stimulus. Serum peak levels of both cytokines were at least halved in VIT-D-deprived mice. Thus, VIT-D deficiency may represent a model of partial defect of monokine production.
Kankova
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Luini
W
W
Pedrazzoni
M
M
Riganti
F
F
Sironi
M
M
Bottazzi
B
B
Mantovani
A
A
Vecchi
A
A
D000818:Animals; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000172:deficiency*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014808:Vitamin D Deficiency / Q000276:immunology*
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D007371:Interferon-gamma