LTB4 increases nasal neutrophil activity and conditions neutrophils to exert antiviral effects.
BACKGROUND
Leukotriene B4 (LTB4) recruits and activates neutrophils. Accordingly, this leukotriene is involved in innate defense actions.


OBJECTIVE
To examine if nasal LTB4 can produce neutrophil activity and to explore whether or not LTB4 can condition neutrophils to exert virucidal effects in vitro and in vivo.


METHODS
1. Twenty-three healthy subjects received nasal LTB4 in a randomized and sham-controlled design. Symptoms were scored and nasal lavages carried out. Myeloperoxidase (MPO) and α-defensins were monitored as indices of neutrophil activity. IL-8, eosinophil cationic protein (ECP) and α(2)-macroglobulin were measured as indices of pro-inflammatory cytokine production, eosinophil activity, and plasma exudation. 2. Supernatants from neutrophils activated by LTB4 in vitro were assayed for virucidal activity against respiratory viruses. 3. In 38 healthy individuals, nasal inoculation with human rhinovirus-16 (HRV-16) was performed. In a preliminary study, intervention with LTB4 was given in a randomized and controlled design. Symptoms, virus replication, and antibody-titres were monitored.


RESULTS
1. LTB4 produced statistically significant increases in MPO and α-defensins, whereas IL-8, ECP, and α(2)-macroglobulin were unaffected. 2. The supernatants efficiently killed human coronavirus, respiratory syncytial virus, and influenza B virus. 3. HRV-16 replication was lower in subjects receiving LTB4, but this difference failed to reach statistical significance. Common cold symptoms and incidence of seroconversion were unaffected.


CONCLUSIONS
Nasal LTB4 induces a selective recruitment/activation of neutrophils. LTB4 can condition neutrophils to exert virucidal effects in vitro and may reduce virus replication in vivo. We suggest that the condition induced by LTB4 reflects an enhanced state of innate defense.
Department of Otorhinolaryngology, Head & Neck Surgery, Clinical Sciences, Lund University Hospital, Getingevägen 4, SE-221 85 Lund, Sweden. henrik.widegren@skane.se
Henrik
H
Widegren
Morgan
M
Andersson
Pierre
P
Borgeat
Louis
L
Flamand
Sebastian
S
Johnston
Lennart
L
Greiff
D000328:Adult; D047150:Eosinophil Cationic Protein / Q000032:analysis; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology* / Q000821:virology; D018375:Neutrophil Activation / Q000187:drug effects* / Q000276:immunology; D009195:Peroxidase / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D023084:alpha-Defensins / Q000032:analysis; D000511:alpha-Macroglobulins / Q000032:analysis
D016209:Interleukin-8; D023084:alpha-Defensins; D000511:alpha-Macroglobulins; D007975:Leukotriene B4; D009195:Peroxidase; D047150:Eosinophil Cationic Protein
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