Generation of TNF alpha, IFN gamma, IL-6, IL-4 and IL-10 in mouse serum from trichinellosis: effect of the anti-inflammatory compound 4-deoxypyridoxine (4-DPD).
Infections caused by the nematode Trichinella spiralis is characterized in the host by an inflammatory response with cytokine production. In these studies we have detected TNF alpha, IL-6, IFN gamma, IL-4 and IL-10 in the serum of 10 mice infected with T. spiralis. Moreover, we detected, for the first time, these cytokines in the serum of mice treated with 4-DPD, a potent antagonist of vitamin B6 coenzyme which has anti-inflammatory properties. 4-DPD was used at 100, 400, 800 micrograms/bolus for 20 days, starting one day before the infection. After 15 days of T. spiralis infection, TNF alpha reached a maximum level, while IL-6 was maximal after 7 days, IFN gamma at 20 days and IL-4 at 14 days. IL-10 was not affected by the T. spiralis infection. When the animals were treated with 4-DPD at the reported dosages and infected with T. spiralis the inhibition of TNF alpha and IL-6, were dose-dependent in the first 7 days while IL-4 was reduced only at 400-800 micrograms/bolus. 4-DPD-treated mice did not statistically (P > 0.05) affect the generation of IFN gamma. In healthy animals the production of cytokines were not measurable, just as it was in non-infected animals treated with 4-DPD. The increase of cytokines such as, TNF alpha and IL-6 may be related to the severity of the disease, boosting the host's resistance to the pathogen and inhibiting parasite survival. In addition, the augmentation of IL-4 production enhances T and B cells and macrophage responses and may stimulate T-cell antibody-mediated response to the pathogen. 4-DPD, an inhibitor of IL-1 and inflammatory reactions, proved to be most effective on TNF alpha and IL-6, which are mainly produced by macrophages.
Frydas
S
S
Laboratory of Parasitology and Parasitic Diseases, Veterinary Faculty, Aristotle University of Thessaloniki, Greece.
Karagouni
E
E
Dotsika
E
E
Reale
M
M
Barbacane
R C
RC
Vlemmas
I
I
Anogianakis
G
G
Trakatellis
A
A
Conti
P
P
D000818:Animals; D000871:Anthelmintics; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000871:Anthelmintics; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; C004675:4-deoxypyridoxine; D007371:Interferon-gamma; D011736:Pyridoxine