Ibudilast suppresses TNFα production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS

Regulating Factors for Microglial Activation.

“…80) Some other reagents that increase cAMP levels also have inhibitory effects. Phosphodiesterase inhibitors, such as propentofylline 79) and ibudilast, 81) inhibit LPS-induced TNFa production. Vasoactive intestinal peptide (VIP) and its related peptide, pituitary adenylyl cyclase-activating polypeptide (PACAP) show inhibitory effects on LPS-induced TNFa expression.…”

Opportunities for the Development of Neuroimmune Therapies in Addiction

“…Ibudilast (IBUD; MN-166/AV411) is a nonselective phosphodiesterase inhibitor with preferential inhibition of PDE3A, PDE4, PDE10, and PDE11 (Gibson et al, 2006) that also inhibits glial cell activation (Suzumura, Ito, Yoshikawa, & Sawada, 1999) and production of macrophage migration inhibitory factor (Cho et al, 2010). IBUD has been used clinically for over 20 years in Asia for the treatment of bronchial asthma and, more recently, for poststroke dizziness and ocular allergies for which it has proven to be safe and well tolerated (Rolan, Hutchinson, & Johnson, 2009).…”

“…IBUD increases expression of GDNF in in vitro studies (Mizuno et al, 2004) suggesting that IBUD may ameliorate DA dysfunction among MA users and alcohol-dependent patients via the induction of GDNF expression. IBUD also reduces microglial activation in vitro in preclinical studies (Suzumura, Ito, & Mizuno, 1999Suzumura et al, 1999). IBUD dosedependently protected against microglial activation and the subsequent cerebrovascular white matter lesions following bilateral ligation of the carotid arteries (an animal model of vascular dementia/cognitive impairment) in rats (Wakita et al, 2003).…”

Role of Microglia in Inflammatory Process in Parkinson’s Disease

“…Pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 are pleiotropic, and may produce either neurotoxic or neuroprotective effects (Arai et al, 2004;Barger et al, 1995;Bolin et al, 2002;Fisher et al, 2001;Liu et al, 1998;Mason et al, 2001;McGuire et al, 2001). TNF-α produced by microglia or astrocytes in the CNS is generally considered to be neurotoxic (Sawada M. et al, 1989;Suzumura et al, 1999). Microglial production of TNF-α is increased when the cells are stimulated with lipopolysaccharide (LPS; Sawada M. et al, 1989Sawada M. et al, , 1995.…”