Type I IL-1 receptor blockade exacerbates murine listeriosis.
It was found that IL-1 is produced in livers and spleens of mice shortly after the i.v. injection of a sublethal or lethal Listeria monocytogenes inoculum. In sublethally infected mice, IL-1 was present in infected livers and spleens by the end of the first day of infection. Thereafter, the amounts of IL-1 in these organs increased and decreased in concordance with bacterial numbers. IL-1 was not present in the peripheral circulation of mice during sublethal listeriosis, but was present in the blood late in lethal infection. Evidence showing that IL-1 plays a role in antibacterial resistance early in listeriosis was obtained through the use of 35F5 mAb that binds to the murine type I IL-1R and functions to block IL-1 alpha and IL-1 beta actions. Blockade of the type I IL-1R by the 35F5 mAb results in greatly enhanced bacterial growth in the livers and spleens of mice that had received a sublethal Listeria inoculum. Consistent with the exacerbation of listeriosis caused by 35F5 mAb, but in contrast to the effect of 35F5 mAb in other murine models, 35F5 mAb-treated mice exhibit markedly elevated levels of IL-6 in their circulation and infected organs.
Havell
E A
EA
Trudeau Institute, Inc., Saranac Lake, NY 12983.
Moldawer
L L
LL
Helfgott
D
D
Kilian
P L
PL
Sehgal
P B
PB
D000818:Animals; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008088:Listeriosis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1; D012709:Serum Albumin / Q000032:analysis; D000683:Serum Amyloid P-Component / Q000032:analysis; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D012709:Serum Albumin; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha