TY - JOUR
T1 - The potential therapeutic role of interleukin-12 in cutaneous T-cell lymphoma
AU - Rook, Alain H.
AU - Kubin, Marek
AU - Fox, Floyd E.
AU - Niu, Zhutian
AU - Cassin, Maureen
AU - Vowels, Benjamin R.
AU - Gottleib, Scott L.
AU - Vonderheid, Eric C.
AU - Lessin, Stuart R.
AU - Trinchieri, Giorgio
PY - 1996
Y1 - 1996
N2 - Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative disorder characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature T-helper (Th) cells. Sezary syndrome (SzS) represents an advanced form of CTCL associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by peripheral blood mononuclear cells (PBMCs) in SzS characterized by increased IL-4 and deficient IL-2 and IFN-γ production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, indicating that the clonal T-cell population is likely derived from the T-helper type 2 (Th2) subset of helper T lymphocytes. Furthermore, a variety of immune abnormalities have been observed in association with SzS that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-γ production and causes the activation of cytotoxic lymphocytes, we assessed the production of IL-12 by PBMCs from SzS patients, and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and, thus, possibly lead to correction of immune defects. In this review, we present our data, which indicate that patients with SzS exhibit marked defects in monocyte production of IL-12 p70. Moreover, in vitro culture of PBMC from SzS patients with recombinant IL-12 leads to reconstitution of normal IFN-γ production and markedly enhances cell-mediated cytotoxicity.
AB - Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative disorder characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature T-helper (Th) cells. Sezary syndrome (SzS) represents an advanced form of CTCL associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by peripheral blood mononuclear cells (PBMCs) in SzS characterized by increased IL-4 and deficient IL-2 and IFN-γ production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, indicating that the clonal T-cell population is likely derived from the T-helper type 2 (Th2) subset of helper T lymphocytes. Furthermore, a variety of immune abnormalities have been observed in association with SzS that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-γ production and causes the activation of cytotoxic lymphocytes, we assessed the production of IL-12 by PBMCs from SzS patients, and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and, thus, possibly lead to correction of immune defects. In this review, we present our data, which indicate that patients with SzS exhibit marked defects in monocyte production of IL-12 p70. Moreover, in vitro culture of PBMC from SzS patients with recombinant IL-12 leads to reconstitution of normal IFN-γ production and markedly enhances cell-mediated cytotoxicity.
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U2 - 10.1111/j.1749-6632.1996.tb52680.x
DO - 10.1111/j.1749-6632.1996.tb52680.x
M3 - Article
C2 - 8958942
AN - SCOPUS:17344388275
SN - 0077-8923
VL - 795
SP - 310
EP - 318
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -