Biomaterial Database

Failure of salmeterol to inhibit circulating white cell responses and bronchoconstriction induced by platelet activating factor. 1992

J Spring, and S R Johnston, and J Seale, and P W Ind

Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London.

BACKGROUND Platelet activating factor (PAF) is a potent mediator of inflammation. Inhalation of PAF causes acute bronchoconstriction and a transient fall in white blood cell count in humans. Salmeterol inhibits pulmonary inflammation induced by PAF in guinea pigs. METHODS The effect of salmeterol on effects induced by PAF was investigated in eight normal subjects who inhaled salmeterol (50 micrograms) twice daily or a matched placebo for one week before challenge with PAF. Blood samples were taken from a forearm catheter for total white cell and neutrophil counts before and for 30 minutes after administration of PAF (48 micrograms) through a Mefar dosimeter. Blood films were stained for unsegmented neutrophils before and after treatment with PAF on a placebo day. RESULTS Mean baseline total white cell counts and neutrophil counts did not differ on the two days. Mean baseline sGaw was significantly higher after inhaled salmeterol (1.84 (95% C1 1.45-2.23) s-1kPa-1) than after placebo (1.53 (1.24-1.82)). After placebo mean total white cell counts, neutrophil counts, and sGaw were reduced to 60 (43-78)%, 39 (14-64)%, and 82 (71-93)% of baseline respectively five minutes after inhaled PAF. After salmeterol treatment mean reductions five minutes after inhaled PAF were 59 (45-73)%, 40 (19-61)%, and 82 (71-93)% of baseline respectively. At 30 minutes after treatment with PAF the neutrophil count rebounded to 143 (82-204)% of baseline after placebo and to 127 (93-161)% after inhaled salmeterol. There was no significant difference in the percentage of immature neutrophils before and after treatment with PAF (2.0 (0.5-2.6)% compared with 3.9 (2.2-5.6)%. CONCLUSIONS Treatment with salmeterol did not inhibit reduction in total white cell count or neutrophil count, rebound neutrophilia, acute bronchoconstriction, or transient flushing after inhalation of PAF. These results conflict with the inhibitory effect of salmeterol on lung inflammation in guinea pigs but are consistent with the lack of effect of salbutamol in humans. Salmeterol does not have an anti-PAF effect in vivo in humans.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007958	Leukocyte Count	The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.	Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008214	Lymphocytes	White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.	Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008231	Lymphopenia	Reduction in the number of lymphocytes.	Lymphocytopenia,Lymphocytopenias,Lymphopenias
D008297	Male		Males
D009504	Neutrophils	Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.	LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D010972	Platelet Activating Factor	A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.	AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D004311	Double-Blind Method	A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.	Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man