A plausible explanation for the contradictory findings is that the classic signaling pathway is anti-inflammatory and the trans-signaling pathway is proinflammatory, and the effects of the two pathways may counteract each other in IL-6-knockout mice following obstructive injury; although renal fibrosis might be reduced due to the absence of proinflammatory trans-signaling, injured renal tissue also lacks the anti-inflammatory effects of classic IL-6 signaling, and fibrosis can probably be exacerbated by an increase in other inflammatory processes 59. This evidence concerns the gene IL6 and renal fibrosis.