Interleukin-8 stimulates human immunodeficiency virus type 1 replication and is a potential new target for antiretroviral therapy.
Production of the C-X-C chemokines interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-alpha) in macrophages is stimulated by exposure to human immunodeficiency virus type 1 (HIV-1). We have demonstrated previously that GRO-alpha then stimulates HIV-1 replication in both T lymphocytes and macrophages. Here we demonstrate that IL-8 also stimulates HIV-1 replication in macrophages and T lymphocytes. We further show that increased levels of IL-8 are present in the lymphoid tissue of patients with AIDS. In addition, we demonstrate that compounds which inhibit the actions of IL-8 and GRO-alpha via their receptors, CXCR1 and CXCR2, also inhibit HIV-1 replication in both T lymphocytes and macrophages, indicating potential therapeutic uses for these compounds in HIV-1 infection and AIDS.
Lane
B R
BR
Divisions of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0640, USA.
Lore
K
K
Bock
P J
PJ
Andersson
J
J
Coffey
M J
MJ
Strieter
R M
RM
Markovitz
D M
DM
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D000906:Antibodies / Q000276:immunology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000821:virology*; D009000:Monocytes; D010671:Phenylurea Compounds / Q000494:pharmacology; D023062:Receptors, Interleukin-8A / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000276:immunology; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
D000906:Antibodies; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D010671:Phenylurea Compounds; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C112019:SB 225002