TY - JOUR
T1 - Are cytokine gene polymorphisms related to in vitro cytokine production profiles?
AU - Warlé, Michiel C.
AU - Farhan, Ayar
AU - Metselaar, Herold J.
AU - Hop, Wim C J
AU - Perrey, Chris
AU - Zondervan, Pieter E.
AU - Kap, Marcel
AU - Kwekkeboom, Jaap
AU - Ijzermans, Jan N M
AU - Tilanus, Hugo W.
AU - Pravica, Vera
AU - Hutchinson, Ian V.
AU - Bouma, Gerda J.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Currently, there is much interest in the genetic basis for diseases or disease manifestations and, in particular, in whether they are related to cytokine gene polymorphisms. It has become accepted to denote such single-nucleotide polymorphisms of cytokine genes by their presumed association with high or low in vitro cytokine production. In this article, we analyze the relationship between cytokine gene polymorphisms and in vitro tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL)-10 and IL-13 production, both in liver transplant recipients and in healthy volunteers. The evaluated cytokine gene polymorphisms involved TNF-A-308; TNF-d3; IFN-G+874; IL-10-1082, -819, and -592; and IL-13+2043, and -1055. For healthy volunteers, we observed a relationship between polymorphisms of TNF-d3 and IL-10-1082 with in vitro production of TNFα and IL-10, respectively, whereas no significant associations were found for the other tested cytokine gene polymorphisms. For liver transplant recipients, no significant relationship could be established between any of the cytokine gene polymorphisms and in vitro production of corresponding cytokines. Also, we reviewed the literature for the association between cytokine gene polymorphisms and in vitro cytokine production in various patient groups and healthy volunteers. We found that the cellular sources, from which the cytokines were released into the culture supernatant, were different between studies. They were either whole blood, isolated monocytes, or peripheral blood mononuclear cells (PBMC). Also, the in vitro incubation protocol varied to a great extent between studies. This applied for the used in vitro stimulant, the concentration of a particular stimulant, and the length of the incubation period. Moreover, the study populations were either healthy individuals or very diverse patient groups. Therefore, it was impossible to evaluate whether in vitro cytokine production profiles really can be deduced from a particular cytokine gene polymorphism. Given the inconclusive findings, we propose to set up a multicenter workshop in which the relationship between certain cytokine gene polymorphisms and in vitro cytokine production is analyzed, using an identical in vitro cell culture system and study population. Furthermore, we suggest that cytokine gene polymorphisms be described by their localization within the gene or gene-promoter, rather than by their presumed in vitro cytokine production profile, to properly evaluate the relationship between cytokine gene polymorphisms and disease manifestations.
AB - Currently, there is much interest in the genetic basis for diseases or disease manifestations and, in particular, in whether they are related to cytokine gene polymorphisms. It has become accepted to denote such single-nucleotide polymorphisms of cytokine genes by their presumed association with high or low in vitro cytokine production. In this article, we analyze the relationship between cytokine gene polymorphisms and in vitro tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL)-10 and IL-13 production, both in liver transplant recipients and in healthy volunteers. The evaluated cytokine gene polymorphisms involved TNF-A-308; TNF-d3; IFN-G+874; IL-10-1082, -819, and -592; and IL-13+2043, and -1055. For healthy volunteers, we observed a relationship between polymorphisms of TNF-d3 and IL-10-1082 with in vitro production of TNFα and IL-10, respectively, whereas no significant associations were found for the other tested cytokine gene polymorphisms. For liver transplant recipients, no significant relationship could be established between any of the cytokine gene polymorphisms and in vitro production of corresponding cytokines. Also, we reviewed the literature for the association between cytokine gene polymorphisms and in vitro cytokine production in various patient groups and healthy volunteers. We found that the cellular sources, from which the cytokines were released into the culture supernatant, were different between studies. They were either whole blood, isolated monocytes, or peripheral blood mononuclear cells (PBMC). Also, the in vitro incubation protocol varied to a great extent between studies. This applied for the used in vitro stimulant, the concentration of a particular stimulant, and the length of the incubation period. Moreover, the study populations were either healthy individuals or very diverse patient groups. Therefore, it was impossible to evaluate whether in vitro cytokine production profiles really can be deduced from a particular cytokine gene polymorphism. Given the inconclusive findings, we propose to set up a multicenter workshop in which the relationship between certain cytokine gene polymorphisms and in vitro cytokine production is analyzed, using an identical in vitro cell culture system and study population. Furthermore, we suggest that cytokine gene polymorphisms be described by their localization within the gene or gene-promoter, rather than by their presumed in vitro cytokine production profile, to properly evaluate the relationship between cytokine gene polymorphisms and disease manifestations.
U2 - 10.1053/jlts.2002.50014
DO - 10.1053/jlts.2002.50014
M3 - Article
C2 - 12548511
VL - 9
SP - 170
EP - 181
JO - Liver Transplantation
JF - Liver Transplantation
SN - 1527-6465
IS - 2
ER -