Expression of interleukin-12 is increased in psoriatic skin.

Although the precise underlying pathomechanisms of psoriasis have not been fully elucidated, previous reports suggest that T helper 1-type cytokines are critically involved in the pathogenesis of this disease. Interleukin-12 (IL-12), a heterodimeric cytokine, has been suggested to play a major role in the development of T helper 1 cell responses. In this study, the presence of IL-12 mRNA and protein was investigated in normal human skin as well as nonlesional and lesional psoriatic skin. Messenger RNA levels were determined in biopsy specimens by a standard and a nested reverse transcriptase-polymerase chain reaction method. Additionally, IL-12 protein expression was analyzed in situ by immunohistochemistry using an antibody recognizing IL-12 p70. Whereas specific transcripts for IL-12 p35 were reproducibly detected without any significant differences in all samples, enhanced IL-12 p40 mRNA signals were only found in lesional psoriatic skin as compared with normal and nonlesional psoriatic skin. Furthermore, immunoreactivity for IL-12 p70 was markedly increased in the psoriatic skin lesions and was predominantly expressed on mononuclear cells in the dermis. In conclusion, our data suggest a critical role for IL-12 in promoting and maintaining T cell activation and inducing T helper 1-type cytokines such as interferon-gamma in psoriasis. We speculate that IL-12 might be a key cytokine in the pathogenesis of psoriasis.

[1]  L. Adorini,et al.  Targeting IL-12, the key cytokine driving Th1-mediated autoimmune diseases. , 1997, Chemical immunology.

[2]  J. Garioch,et al.  Restricted T‐cell receptor Vβ gene usage in the skin of patients with guttate and chronic plaque psoriasis , 1993, The British journal of dermatology.

[3]  W Sterry,et al.  IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. , 1998, The Journal of clinical investigation.

[4]  M. Fey,et al.  Interleukin-12 expression in human lymphomas and nonneoplastic lymphoid disorders. , 1995, Blood.

[5]  D. Macdonald,et al.  Increased epidermal cell proliferation in normal human skin in vivo following local administration of interferon-gamma. , 1993, The American journal of pathology.

[6]  M. Heng,et al.  Cell interactions in psoriasis. , 1985, Archives of dermatology.

[7]  I. Jónsdóttir,et al.  Circulating T Cells of Patients with Active Psoriasis Respond to Streptococcal M‐Peptides Sharing Sequences with Human Epidermal Keratins , 1997, Scandinavian journal of immunology.

[8]  E. Minshall,et al.  In vivo expression of IL-12 and IL-13 in atopic dermatitis. , 1996, The Journal of allergy and clinical immunology.

[9]  E. Christophers The immunopathology of psoriasis. , 1996, International archives of allergy and immunology.

[10]  H. Valdimarsson,et al.  Epidermal T lymphocytes and HLA‐DR expression in psoriasis , 1984, The British journal of dermatology.

[11]  A. Menssen,et al.  Evidence for an antigen-specific cellular immune response in skin lesions of patients with psoriasis vulgaris. , 1995, Journal of immunology.

[12]  M. Yamamura,et al.  The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response. , 1993, The Journal of investigative dermatology.

[13]  A. Lanzavecchia,et al.  Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation , 1996, The Journal of experimental medicine.

[14]  G. Rassner,et al.  Psoriasis induced at the injection site of recombinant interferon gamma. Results of immunohistologic investigations. , 1990, Archives of dermatology.

[15]  G. Trinchieri,et al.  Immunomodulatory functions and molecular regulation of IL-12. , 1997, Chemical immunology.

[16]  N. Yawalkar,et al.  Constitutive expression of both subunits of interleukin-12 in human keratinocytes. , 1996, The Journal of investigative dermatology.

[17]  Richard E. Goodman,et al.  Interleukin 12: A Potential Link between Nerve Cells and the Immune Response in Inflammatory Disorders , 1995, Molecular medicine.

[18]  L. Kowalzick,et al.  Psoriasis induced at the injection site of recombinant interferons. , 1990, Archives of dermatology.

[19]  H. Nariuchi,et al.  Induction of IL-12 p40 messenger RNA expression and IL-12 production of macrophages via CD40-CD40 ligand interaction. , 1996, Journal of immunology.

[20]  J. Travers,et al.  Lymphocyte activation in the pathogenesis of psoriasis. , 1997, The Journal of investigative dermatology.

[21]  G. Trinchieri Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. , 1995, Annual review of immunology.

[22]  W. Jochum,et al.  T cells involved in psoriasis vulgaris belong to the Th1 subset. , 1994, The Journal of investigative dermatology.

[23]  N. Romani,et al.  High Level IL-12 Product ion by Murine Dendrit ic Cells : Upregulation via MHC Class II and CD 40 Molecules and Downregulat ion by IL-4 and IL-10 By , 2003 .

[24]  I. Jónsdóttir,et al.  Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens? , 1995, Immunology today.

[25]  M. Degré,et al.  Interferon in suction blister fluid from psoriatic lesions , 1983, The British journal of dermatology.

[26]  C. Maliszewski,et al.  Activated T cells induce interleukin‐12 production by monocytes via CD40‐CD40 ligand interaction , 1995, European journal of immunology.

[27]  P. Kerkhof,et al.  Transition from symptomless to lesional psoriatic skin , 1996, Clinical and experimental dermatology.

[28]  A. Menssen,et al.  T lymphocytes derived from skin lesions of patients with psoriasis vulgaris express a novel cytokine pattern that is distinct from that of T helper type 1 and T helper type 2 cells , 1994, European journal of immunology.

[29]  L. Picker,et al.  Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production , 1995, The Journal of experimental medicine.

[30]  M. Gately,et al.  Analysis of the multiple interactions between IL-12 and the high affinity IL-12 receptor complex. , 1998, Journal of immunology.