Primary immune response in skin and skin-associated lymphoid tissue of interleukin-4 transgenic mice.
The interleukin-4 transgenic mice investigated here exhibit a ubiquitous expression of interleukin-4 in all organs, including the skin. In this study, the induction phase of oxazolone-induced local primary contact hypersensitivity and croton oil-induced irritant contact dermatitis in transgenic and wild-type mice was analysed. Compared to wild-type mice, the transgenic mice showed a decreased activation of the skin-draining lymph nodes but a strong hyperreactivity in the skin after topical sensitisation. In contrast to this, both the transgenic and the wild-type mice developed a strong and comparable inflammatory skin reaction after topical irritation. A striking increased expression level of tumour necrosis factor-alpha and macrophage inflammatory protein-2 genes were found in the skin of the transgenic mice during primary local contact hypersensitivity, while both the transgenic and the wild-type mice developed comparable expression levels of these cytokines during irritant contact dermatitis. Compared to wild-type mice, a strongly enhanced expression level of interleukin-6 transcripts derived from epidermal antigen presenting cells were detected in the skin of IL-4 transgenic mice, whereas in the skin-draining lymph nodes of transgenic mice significantly lower levels were detected. We conclude that the migration of epidermal antigen-presenting cells towards the skin-draining lymph nodes is reduced in transgenic mice, which could be due to the different cytokine balance in these mice strains. The atypical irritant-like reaction observed in transgenic mice after topical sensitisation is a phenomenon comparable to atopic diseases and therefore this transgenic strain might be a helpful model for investigating the immunopathophysiological features of these diseases.
Blümel
J
J
Institute of Toxicology, Bayer AG, 42096 Wuppertal, Germany.
Schimpl
A
A
Ulrich
P
P
Ahr
H J
HJ
Vohr
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D054426:Chemokine CXCL2; D003436:Croton Oil / Q000008:administration & dosage / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology; D004423:Ear; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015846:Monokines / Q000235:genetics; D010081:Oxazolone / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D054426:Chemokine CXCL2; D015850:Interleukin-6; D015846:Monokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone; D015847:Interleukin-4; D003436:Croton Oil