Histopathologic evidence of peptide-mediated disease modulation. H&E-stained representative ankle sections from Tg197 mice (a) without treatment, or after treatment with (b) 10 mg/kg and (c) 30 mg/kg of phospholipase inhibitor from python (PIP)-18, respectively for five weeks (n = 16 joints/group). The extent of synovial hyperplasia (sh), cartilage degradation (cd), and bone erosion (be) was less marked in the joints of (b, c) peptide-treated group than in (a) untreated joints, with histologic appearance more or less similar to that seen in the (d) infliximab treated or (e) normal (wild type) joints. Note the less marked hyperplasia (arrow), cartilage destruction (*) and bone erosion (arrowhead) in the representative joint of (c) 30 mg/kg PIP-18-treated group compared with that of (b) 10 mg/kg PIP-18-treated group. b = bone; be = bone erosion; c = cartilage; cd = cartilage degradation; jc = joint cavity; sh = synovial hyperplasia. (f) Mean histopathologic scores (HS) are shown for different treatment groups. Compared with untreated mice, P-NT.II, PIP-18 and infliximab treatment significantly decreased HS (**P < 0.001) as did treatment with antiflammin-2, methotrexate (Mtx), and celecoxib (Cxb), which were less effective (*P < 0.01). Higher dose (30 mg/kg) of PIP-18 was more effective than the lower dose (10 mg/kg) (*P < 0.01). One-way analysis of variance with Bonferroni's multiple comparison post test. Bars = 500 μm. Infliximab (10 mg/kg) and 30 mg/kg PIP-18 had similar modulatory effect on HS (P > 0.05, two-tailed paired t-test).