On radiation damage to normal tissues and its treatment. II. Anti-inflammatory drugs.
In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (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 H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A2 whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cyclooxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodromal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable.
Michalowski
A S
AS
MRC Cyclotron Unit, Hammersmith Hospital, London, UK.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002450:Cell Communication / Q000528:radiation effects*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D015777:Eicosanoids / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000528:radiation effects; D011464:Epoprostenol / Q000096:biosynthesis; D005938:Glucocorticoids / Q000494:pharmacology; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011453:Prostaglandins / Q000096:biosynthesis; D011832:Radiation Injuries / Q000188:drug therapy* / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects; D013931:Thromboxanes / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D005938:Glucocorticoids; D015289:Leukotrienes; D011453:Prostaglandins; D013931:Thromboxanes; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2