Cytokine response to endotoxin in individuals heterozygous for the Delta32 mutation of chemokine receptor CCR5.
Studies of mice with a targeted disruption of the CCR5 gene suggest that the CC chemokine receptor 5 (CCR5) is a determinant of the cytokine response to endotoxin. In humans, a naturally occurring mutation of the CCR5 gene is a 32-basepair (bp) deletion which precludes the translation of the gene into a functional transmembrane protein. To evaluate the cytokine phenotype of heterozygosity for the 32 deletion, we studied the endotoxin-stimulated release of tumor necrosis factor-alpha, Interleukin (IL)-6, IL-8, IL-10, and IL-12 in whole blood ex-vivo of healthy volunteers and patients undergoing elective cardiac bypass surgery. This operation represents a major surgical trauma associated with ischemia-reperfusion-injury and triggers a profound inflammatory response. In these patients, cytokine plasma concentrations were measured during and after cardiac surgery. No difference was found between the frequencies of the observed and expected CCR5 genotypes in the groups of individuals studied. Furthermore, no significant difference in ex-vivo or peri- and postoperative cytokine plasma concentrations was detected between CCR5 wild-type homozygotes and individuals carrying one defective CCR5 allele. Our results indicate that heterozygosity for the 32bp deletion of CCR5 is not associated with an altered cytokine response to endotoxin or to a major surgical trauma when compared with individuals homozygous for the wild-type allele.
Heesen
Michael
M
Department of Anesthesia, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands. m.heesen@amc.uva.nl
Schippers
Emile F
EF
Bloemeke
Brunhilde
B
Kunz
Dagmar
D
van Dissel
Jaap T
JT
D000328:Adult; D000368:Aged; D000483:Alleles; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000494:pharmacology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007378:Interleukins / Q000097:blood; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D044465:White People
D016207:Cytokines; D004731:Endotoxins; D007378:Interleukins; D019713:Receptors, CCR5; D014409:Tumor Necrosis Factor-alpha