Radiation and inflammation

Abstract

The immune system has the power to modulate the expression of radiation-induced normal and tumor tissue damage. On the one hand, it can contribute to cancer cure, and on the other hand, it can influence acute and late radiation side effects, which in many ways resemble acute and chronic inflammatory disease states. The way radiation-induced inflammation feeds into adaptive antigen-specific immune responses adds another dimension to the tumor-host cross talk during radiation therapy and to possible radiation-driven autoimmune responses. Understanding how radiation affects inflammation and immunity is therefore critical if we are to effectively manipulate these forces for benefit in radiation oncology treatments.

Figure 1

Nrf2 prevents excessive Th1 signaling in activated T cells. Splenocytes were isolated from Nrf2−/− mice and stimulated in vitro with aCD3/CD28 with or without LPS. IL-4 and IFN-γ releasing splenocytes were enumerated 36h later by ELISPOT and compared to splenocyte responses from C57Bl/6 WT mice.

Figure 2

Radiation primes macrophages for pro-inflammatory signaling when given prior to TLR engagement. RAW264.7 murine macrophages were stimulated with 10ng/ml LPS either 30mins before or after X-irradiation. Supernatants were harvested after 4h of stimulation and assayed for TNF-α production by ELISA.

Figure 3

Inhibition of HMGB-1 aids the recovery of whole-body irradiated mice. Male C3H mice were lethally irradiated with 8Gy and treated with s.c. 330mg/kg Glycyrrhizin everyday for 5 days starting 24h post exposure. Survival was monitored over 30days. N=8 animals/group.

Figure 4

Recurring waves of inflammation link radiation-induced tissue damage to anti-tumor immune activation with potentially excessive normal tissue damage. This is being offset by attempts to resolve the inflammatory lesion, to heal and to regulate immunity at the price of possible tumor immune escape. Black (tumor), red (inflammation), green (healing).