The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1β), and complement.
Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1β), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1β and MIP-1β/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1β; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.
Respiratory Clinical Trials Ltd, London, UK.
B R
BR
Leaker
Merck Research Laboratories, Rahway, New Jersey, USA.
V A
VA
Malkov
Merck Research Laboratories, Rahway, New Jersey, USA.|Present address: Celgene (L.N.C. and G.C.); Janssen R & D, Spring House, PA (R.M.); Alnylam (M.K.R.); Novartis (C.T.); GSK (N.A.C.); Otsuka (H.C.).
R
R
Mogg
Merck Research Laboratories, Rahway, New Jersey, USA.|Present address: Celgene (L.N.C. and G.C.); Janssen R & D, Spring House, PA (R.M.); Alnylam (M.K.R.); Novartis (C.T.); GSK (N.A.C.); Otsuka (H.C.).
M K
MK
Ruddy
Respiratory Clinical Trials Ltd, London, UK.
G C
GC
Nicholson
Imperial Clinical Respiratory Research Unit (ICRRU), St Mary's Hospital, Imperial College, London, UK.
A J
AJ
Tan
Merck Research Laboratories, Rahway, New Jersey, USA.|Present address: Celgene (L.N.C. and G.C.); Janssen R & D, Spring House, PA (R.M.); Alnylam (M.K.R.); Novartis (C.T.); GSK (N.A.C.); Otsuka (H.C.).
C
C
Tribouley
Merck Research Laboratories, Rahway, New Jersey, USA.|Present address: Celgene (L.N.C. and G.C.); Janssen R & D, Spring House, PA (R.M.); Alnylam (M.K.R.); Novartis (C.T.); GSK (N.A.C.); Otsuka (H.C.).
G
G
Chen
MSD (Europe) Inc., Brussels, Belgium.
I
I
De Lepeleire
MSD (Europe) Inc., Brussels, Belgium.|Present address: Celgene (L.N.C. and G.C.); Janssen R & D, Spring House, PA (R.M.); Alnylam (M.K.R.); Novartis (C.T.); GSK (N.A.C.); Otsuka (H.C.).
N A
NA
Calder
Present address: Celgene (L.N.C. and G.C.); Janssen R & D, Spring House, PA (R.M.); Alnylam (M.K.R.); Novartis (C.T.); GSK (N.A.C.); Otsuka (H.C.).
H
H
Chung
Department of Asthma, Allergy and Respiratory Science, King's College, London, UK.
P
P
Lavender
Merck Research Laboratories, Rahway, New Jersey, USA.|Present address: Celgene (L.N.C. and G.C.); Janssen R & D, Spring House, PA (R.M.); Alnylam (M.K.R.); Novartis (C.T.); GSK (N.A.C.); Otsuka (H.C.).
L N
LN
Carayannopoulos
Imperial Clinical Respiratory Research Unit (ICRRU), St Mary's Hospital, Imperial College, London, UK.
T T
TT
Hansel
D000328:Adult; D000485:Allergens / Q000276:immunology; D052179:Antigens, Plant / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000178:diet therapy / Q000188:drug therapy / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D058847:Inflammasomes / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology; D011241:Prednisone / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult
D000485:Allergens; D052179:Antigens, Plant; D058847:Inflammasomes; D018793:Interleukin-13; D053583:Interleukin-1beta; D015848:Interleukin-5; D003165:Complement System Proteins; D011241:Prednisone