IC50: 0.6 μM (Lysophosphatidic acid acyltransferase)
STAT4

(R)-Lisofylline blocks IL-12-driven Th1 differentiation and T cell proliferation in vitro, yet has no effect on IL-12 secretion from APCs ex vivo or in vitro.

(R)-Lisofylline reduces the impairment of insulin secretion induced by IL-1β in cultured rat islet cells, suppresses IFN-γ production, the onset of diabetes, and macrophage infiltration into islets from NOD mice, as well as Lisofylline improves insulin response and lowers glucose levels in Streptozotocin-treated rats after the oral glucose tolerance test.
(R)-Lisofylline prevents β cell dysfunction in NOD mice by inhibition of STAT4 phosphorylation which interrupts IL-12 signaling. (R)-Lisofylline ameliorates experimental allergic encephalomyelitis in mice.
(R)-Lisofylline also improves survival in mice injected with a lethal dose of LPS and ameliorates sepsis-induced lung injury in minipigs. In rats given IL-1 intratracheally (R)-Lisofylline pretreatment reduces lung leak but does not decrease neutrophil accumulation in lungs.
(R)-Lisofylline also suppresses release of TNF-α in vivo in mice and ex vivo in human blood stimulated with endotoxin derived from Salmonella or Escherichia coli .