Fullerene nanoparticles ("Fullerenes"), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1,6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-alpha. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-kappa B and NFAT in splenocytes at 6 days post-administration. Finally, CD11b(+) cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system. (C) 2011 Elsevier B.V. All rights reserved.