Radioprotection by N-palmitoylated nonapeptide of human interleukin-1beta.
Interleukin-1beta (IL-1beta) is a cytokine involved in homeostatic processes of the immune system and specifically in inflammatory reactions. The nonapeptide of human IL-1beta (VQGEESNDK, position 163-171) has been shown to retain adjuvant and immunostimulatory activities of the native molecule without any inflammatory and pyrogenic properties. A lipophilic derivative of IL-1beta nonapeptide having a palmitoyl residue at the amino terminus was synthesized in order to determine the effects of such structural modification on its bioactivities. The structurally modified peptide derivative, palmitoylated peptide, significantly protected C3H/HeN mice against potentially lethal doses of ionizing radiation. The dose reduction factor was found to be 1.07. Hematological studies show improved recovery of red blood cells and platelets in irradiated and palmitoylated peptide treated mice as compared with the untreated and irradiated group. These results suggest the importance of the derivatization of small peptides of radioprotective, but toxic cytokines in order to enhance radioprotective activity while reducing unwanted toxic side effects.
Singh
Vijay K
VK
Radiation Casualty Management Team, Radiation Medicine Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA. singh@afrri.usuhs.mil
Srinivasan
Venkataraman
V
Seed
Thomas M
TM
Jackson
William E
WE
Miner
Venita E
VE
Sree Kumar
K
K
D000276:Adjuvants, Immunologic; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007375:Interleukin-1; D010455:Peptides; D011837:Radiation-Protective Agents; D019308:Palmitic Acid