Cytokine production by human leukocytes with different expressions of natural antiviral immunity and the effect of antibodies against interferons and TNF-alpha.
BACKGROUND
Two activities of innate antiviral immunity were studied: the resistance of human peripheral blood mononuclear cells (PMBCs) ex vivo to viral infection and the production of cytokines.


METHODS
Samples of blood were taken from healthy blood donors and from persons with frequent infections of the upper respiratory system. PMBCs were isolated by gradient centrifugation. Vesicular stomatitis virus (VSV) was used as the indicatory virus to infect PMBCs. The cytokines: IFN, TNF, and IL-6 were titrated by biological methods and IL-10 by ELISA.


RESULTS
Blood donors were divided for two groups: those with VSV-resistant and those with VSV-sensitive PMBCs and secretion of cytokines by them was compared. The resistant PMBCs produced more cytokines than the sensitive ones. A statistically significant difference, was found only in the case of the IFNs. To examine the contribution of IFNs and TNF in maintaining resistance, leukocytes from both groups were treated with specific anti-cytokine antibodies. The authors' previous study showed that the elimination of spontaneous IFN-alpha, IFN-beta, IFN-gamma, and TNF-alpha from resistant leukocytes resulted in increased VSV replication This indicates the important role of cytokines. In VSV-sensitive PMBCs, anti-IFN-alpha showed the opposite effect (decreased virus replication). In the absence of spontaneous IFN-alpha, disturbances in cytokine production were observed.


CONCLUSIONS
Complete resistance of PMBC to VSV infection is accompanied by higher cytokine release, The paradoxical effect of anti-IFN-alpha on virus replication in leukocytes sensitive to viral infection may be attributed to changes in the cytokine profile balance, i.e. high TNF production by VSV-infected leukocytes and a complete reduction of IL-6 production.
Orzechowska
Beata
B
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wrocław, Poland.
Antoszków
Zenon
Z
Siemieniec
Iwona
I
Lorenc
Maria
M
Jatczak
Bogna
B
Błach-Olszewska
Zofia
Z
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000097:blood / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008875:Middle Aged; D018353:Rhabdoviridae Infections / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007372:Interferons