Depressed IL-1 production by chronic GVHD dermal fibroblasts.
Chronic Graft-versus-Host disease (GVHD) is characterized by overt immunosuppression. In addition, the skin is a major anatomical site affected in chronic GVHD for reasons not yet known. Increased collagen deposition, a mononuclear cell infiltrate in the dermis as well as loss of fat and appendages, are observed in the skin. The inflammatory cytokine IL-1 was shown to affect fibroblast proliferation and secretory activities. In the present study, IL-1 generation by dermal fibroblasts, of chronic GVHD or control mice, was assessed. It was shown that two sequential signals are needed for IL-1 generation by dermal fibroblasts; priming by lymphokines/cytokines followed by a challenge with LPS. A variety of recombinant lymphokines and cytokines (G/M-CSF, IL-2, TNF, IL-1 beta and IFNs alpha, beta and gamma) were shown to be efficient in priming dermal fibroblasts for IL-1 generation. IL-1 activity in dermal fibroblasts, most probably of the IL-1 alpha species, was located in frozen-thawed cell lysates or associated to the cell membrane, though not secreted into the culture fluids. Dermal fibroblasts from chronic GVHD mice manifested a pronounced depression in IL-1 generation upon stimulation with exogenous lymphokines/cytokines and LPS. This was observed over a wide range of concentrations of lymphokines/cytokines and LPS. The depressed ability of chronic GVHD fibroblasts to generate IL-1 was pronounced even after few passages of the cells in vitro, and upon stimulation in culture outside the suppressive milieu of the animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Mekori
Y A
YA
Allergy/Immunology Unit, Meir Hospital, Kfar Saba, Israel.
Huleihel
M
M
Baram
D
D
Apte
R N
RN
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis*; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines; D007375:Interleukin-1; D008222:Lymphokines; D011994:Recombinant Proteins