1 In the presence of genotoxic stress poly(ADP-ribose) polymerase-1 (PARP-1) leads to NAD + and ATP depletion, participating in the pathogenesis of several disorders including in¯ammation. Accordingly, chemical inhibitors of PARP-1 are e cacious anti-in¯ammatories, albeit the underlying molecular mechanisms are still under debate. 2 This study investigated the e ect of the PARP-1 inhibitors 6(5H)-phenanthridinone and benzamide as well as that of benzoic acid, an inactive analogue of benzamide, on development of experimental allergic encephalomyelitis (EAE) in rats. Both 6(5H)-phenanthridinone and benzamide attenuated development of EAE, reducing clinical score, neuroimmune in®ltration and expression of in¯ammatory mediators such as inducible nitric oxide synthase, interleukin-1b and -2, cyclooxygenase-2, tumour necrosis factor-a and interferon-g in the spinal cord of myelin-immunized rats. Importantly, no evidence of NAD + and ATP depletion as well as poly(ADP-ribose) formation was detected in the spinal cord.3 By contrast, a robust formation of poly(ADP-ribose) occurred in B-and T-cell areas in lymph nodes of myelin-immunized rats and was suppressed by the treatment with 6(5H)-phenanthridinone and benzamide. In cultures of activated rat lymphocytes, 6(5H)-phenanthridinone and benzamide reduced the DNA-binding activity of NF-kB and AP-1 and transcription of pro-in¯ammatory cytokines such as interleukin-2, interferon-g and tumour necrosis factor-a. 4 Notably, benzoic acid did not reproduce the in vivo and in vitro e ects of its parent compound. 5 These ®ndings indicate that PARP-1 promotes transcriptional activation in lymphocytes and inhibitors of its enzymatic activity are useful for the treatment of autoimmune disorders of the central nervous system.