The invention relates to compositions and methods for inhibiting macrophage activation via modulating PARP9 and/or PARP14 expression or activity, such as small molecules, RNAi and antibodies. Modulating the expression and/or activity of PARP9 and/or PARP14 allows the inhibition of monocytes or macrophage M1 activation and inflammation. Inhibiting undesirable excessive or sustained inflammation found in humans, for the treatment, prevention and/or management of conditions where undesirable excessive or sustained inflammation is known or likely to contribute to the onset, development and/or progression the conditions.