ON RADIATION-DAMAGE TO NORMAL-TISSUES AND ITS TREATMENT .2. ANTIINFLAMMATORY DRUGS

In addition to transiently inhibiting cell cycle progression and steri lizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communic ation (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by assisting a return to normality (e.g., through a rise in II-type cell lineage-s pecific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irra diation and on results of empirical treatment of radiation injuries wi th anti-inflammatory drugs. Prodromal, acute and chronic effects of ra diation are accompanied by excessive production of eicosanoids (prosta glandins, prostacyclin, thromboxanes and leukotrienes). These endogeno us mediators of inflammatory reactions may be responsible for the vaso dilatation, vasoconstriction, increased microvascular permeability, th rombosis and chemotaxis observed after radiation exposure. Glucocortic oids inhibit eicosanoid synthesis primarily by interfering with phosph olipase A, whilst non-steroidal anti-inflammatory drugs prevent prosta glandin/thromboxane synthesis by inhibiting cyclooxygenase. When admin istered after irradiation on empirical grounds, drugs belonging to bot h groups tend to attenuate a range of prodromal, acute and chronic eff ects of radiation in man and animals. Taken together, these two sets o f observations are highly suggestive of a contribution of humoral fact ors to the adverse responses of normal tissues and organs to radiation . A full account of radiation damage should therefore consist of compl ementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal orga ns are justified and desirable.