Further studies on the role of IL-12 in Pseudomonas aeruginosa corneal infection

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Abstract
Purpose Previous studies have shown that in Pseudomonas aeruginosaocular infection, IL-12 drives a Th1 T-cell response and IFN- production in susceptible (cornea perforates) C57BL/6 (B6) mice, and that after similar infection of resistant (cornea heals) BALB/c mice, no IL-12 is detectable in cornea at either the mRNA or protein levels. Therefore, the purpose of this study was to test whether BALB/c mice are capable of responding to exogenous IL-12 administration, and whether disease responsiveness following P. aeruginosachallenge is modified. Methods Immunostaining, RT/PCR, recombinant cytokine injection, and histopathology were used. Statistical analysis was performed using an unpaired, two-tailed Student's t-test. Results Injection of BALB/c mice with recombinant (r) IL-12 converted these normally resistant animals to the susceptible phenotype as evidenced by corneal perforation within 5–7 days after infection. RT-PCR analysis of the corneas of rIL-12 vsPBS/BSA-treated mice showed a significant increase in IFN- and TNF- mRNA levels in the rIL-12 vsPBS/BSA (vehicle)-treated mice at 3 and 5 days p.i. In addition, similar analysis of IL-4 mRNA levels showed decreased amounts of the cytokine in rIL-12 vsvehicle-treated mice. Injection of rIL-4 into susceptible B6 mice, however, failed to rescue these animals from corneal perforation following P. aeruginosachallenge. Conclusions These data provide evidence that BALB/c mice can respond to exogenous IL-12, that the cytokine promotes susceptibility by increasing IFN- and TNF- production, with a concomitant reduction in IL-4 levels; and that injected rIL-4 fails to rescue susceptible B6 mice from corneal perforation after bacterial challenge.