Disease relevance of IL-12

• Treatment of mice with IL-12 at the time of a second antigen challenge also prevented airway hyperresponsiveness and significantly reduced numbers of BAL inflammatory cells, reflecting the ability of IL-12 to inhibit responses associated with ongoing antigen-induced pulmonary inflammation [1].
• Interleukin-12 (IL-12) directs the cognate nephritogenic T helper type 1 responses that initiate renal injury in murine crescentic glomerulonephritis (GN) [2].
• IL-12 chimeric mice showed no attenuation of their systemic cognate immune response to the nephritogenic antigen (sheep globulin), indicated by antigen-specific circulating antibody and cutaneous delayed-type hypersensitivity [2].
• To ensure the equal expression of both subunits, we used the self-cleaving properties of the 2A oligopeptide from foot-and-mouth disease virus (FMDV) to express IL-12 as a single, long open reading frame (ORF) encoding p402Ap35 [3].

High impact information on IL-12

• We used this model to determine the ability of IL-12 to prevent antigen-induced increases in airway hyperresponsiveness, bronchoalveolar lavage (BAL) eosinophils, and lung Th2 cytokine expression [1].
• Administration of IL-12 to CD40(-/-) mice restored Th cell IFN-gamma production, and up-regulated intrarenal chemokines and glomerular T cell and macrophage accumulation compared with WT control mice [4].
• The expression of IL-12 subunits was observed in lymphoid cells and proved to be dependent on the cell type and stimulus, while expression was not detected in stimulated primary chicken embryo fibroblast cells [5].
• The high degree of functional similarity between chicken IL-12 and IL-12 of higher mammalian vertebrates, despite their poor sequence homology, illustrates the conservation and vital importance of the IL-12 molecule since the evolutionary dichotomy of birds and mammals >300 million years ago [5].
• Chimeric IL-12 mice showed significant attenuation of crescent formation, glomerular T-cell and macrophage accumulation, and renal impairment, compared with WT and sham chimeric mice, but were not protected to the same extent as IL-12 -/- mice [2].

Biological context of IL-12

• The results here presented demonstrate, to our knowledge for the first time, a definite role of IL-12 in the induction of a specific antibody response in human cells [6].
• Likewise, S. dublin infection provoked a marked increase of IL-12 mRNA and a slight up-regulation of IFNgamma gene transcription in the local lymphoid site, in contrast to S. abortusovis infection [7].
• IL-12 gene expression in human skin-derived CD1a+ dendritic lymph cells [8].
• Recent reports point to a role for interleukin-12 (IL-12) in regulating T- and NK-cell function, macrophage activation and initiation of Th1-type cell responses [8].
• The protective effect of a Schistosoma japonicum Chinese strain 23 kDa plasmid DNA vaccine in pigs is enhanced with IL-12 [9].

Anatomical context of IL-12

• Secretion of the IL-12 heterodimer from CHO cells co-transfected with ovine p35 and p40 cDNA was shown by immunoprecipitation of a 60 and 66 kDa protein from transfectant supernatant [10].
• To address this possibility, the development of sheep anti-mouse glomerular basement membrane globulin-induced crescentic GN was studied in C57BL/6 wild-type (WT), IL-12-deficient (IL-12 -/-), and IL-12 "chimeric" mice [2].
• The influence of interleukin-12 (IL-12) on the induction of a specific antibody response to the T-dependent antigen sheep erythrocytes (SRBC) in cultures of human blood lymphocytes was investigated [6].
• The response, evaluated as number of antigen-induced antibody-producing cells, was greatly increased in the presence of IL-12 [6].
• Under these latter conditions, since single-hit criteria were fulfilled, it was possible to estimate the frequency of SRBC-specific B cell precursors able to respond to the antigen and to show that such frequency was increased upon addition of IL-12 [6].

Associations of IL-12 with chemical compounds

• When mice were treated with anti-IL-12 prior to inoculation, nitrite levels in splenocyte cultures were reduced by 75% and the suppression of PFC responses was prevented [11].
• MoDCs exposed simultaneously to lipopolysaccharide and ORFV IL-10 showed enhanced ovalbumin-FITC uptake and reduced IL-12 expression, indicating inhibition of maturation [12].

Other interactions of IL-12

• In contrast, there was no change in levels of transcripts for TGFbeta1, IL-1beta, GM-CSF, IL-10, or IL-12 [13].
• Both parameters could be modulated by exogenous recombinant ovine interleukin (IL)-10 and IL-12, but we were unable to correlate IFN-gamma production with endogenous cytokine production in the assays [14].

Analytical, diagnostic and therapeutic context of IL-12

• Local administration of IL-12 may provide a novel immunotherapy for the treatment of pulmonary allergic disorders such as atopic asthma [1].
• The present study investigated the role of interleukin-12 (IL-12) in the generation of nitric oxide-mediated immunosuppression in this model [11].
• IL-12 augmented the capacity of this fraction to suppress PFC responses by normal splenocytes in a coculture system [11].
• The ELISA was also able to detect recombinant ovine IL-12 and, less effectively, recombinant human IL-12 [15].
• The results showed that worm reduction rates in SjC23 group compared with control group were 29.2% and in the SjC23 + IL-12 group reduced 58.6% [9].

References