Selective PDE4 inhibitors also attenuate the development of cyclophosphamide-induced cystitis improving the bladder symptoms, as voiding behaviour and histological damage by suppressing cytokine production and inducible NO synthase induction, and causing a significant decrease on the amplitude and frequency of spontaneous contractions without changing cystometric parameters, thus suggesting that PDE4 inhibitors might be an attractive strategy for the treatment of chemically-induced bladder overactivity42–45. Here, NOS2 is linked to cystitis.