Ibudilast is a non-selective PDE (phosphodiesterase) inhibitor found to have anti-inflammatory activity primarily targeting the peripheral immune system and in the CNS via attenuation of glial cells. Ibudilast is an inhibitor of phosphodiesterase 4 (PDE4; IC50s = 54, 65, 239 and 166nM for PDE4A-D, respectively), PDE3A, PDE3B and PDE5A (IC50s = 1600, 2700 and 3510nM, respectively) and has been shown to act as a toll-like receptor 4 (TLR4) antagonist. Ibudilast is an allosteric inhibitor of macrophage inhibitory factor (MIF), which regulates the immune response known to drive inflammation and the cytokine storm. Overexpression of MIF is linked to multiple disease, including ARDS, asthma, rheumatoid arthritis, lupus and multiple sclerosis. Blocking the effects of MIF can protect patients with COVID-19 from developing ARDS. Ibudilast has bronchodilator, vasodilator (preventing the breakdown of secondary messengers cAMP and cGMP) and neuroprotective/anti-neuroinflammatory effects, is used in asthma and stroke treatment, inhibits platelet aggregation and may be usefull in certain brain disorders. It has been shown to be useful in the treatment of neuropathic pain and reducing methamphetamine, opioid and alcohol addiction. It also has antiviral properties, inhibiting replication of HIV-1.