James E Gern1, Agustin Calatroni2, Katy F Jaffee2, Henry Lynn2, Amy Dresen3, William W Cruikshank4, Howard M Lederman5, Hugh A Sampson6, Wayne Shreffler7, Leonard B Bacharier8, Peter J Gergen9, Diane R Gold10, Meyer Kattan11, George T O'Connor4, Megan T Sandel4, Robert A Wood5, Gordon R Bloomberg8. 1. University of Wisconsin School of Medicine and Public Health, Madison, Wis. Electronic address: gern@medicine.wisc.edu. 2. Rho Inc, Chapel Hill, NC. 3. University of Wisconsin School of Medicine and Public Health, Madison, Wis. 4. Boston University School of Medicine, Boston, Mass. 5. Johns Hopkins University School of Medicine, Baltimore, Md. 6. Icahn School of Medicine at Mount Sinai, New York, NY. 7. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Mass. 8. Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo. 9. National Institute of Allergy and Infectious Diseases, Bethesda, Md. 10. The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medicine School, Boston, Mass. 11. Columbia University Medical Center, New York, NY.
Abstract
BACKGROUND: Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity. OBJECTIVE: We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization. METHODS: A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age. Cytokine responses were measured in blood cell samples obtained at birth (cord blood) and ages 1 and 3 years. Cytokine responses were examined in relation to personal characteristics and environmental exposures to allergens and endotoxin and to the development of allergic sensitization and recurrent wheeze assessed at age 3 years. RESULTS: Cytokine responses generally increased with age, but responses at birth were poorly predictive for those at ages 1 and 3 years. Exposure to certain allergens (cockroach, mouse, dust mite) was significantly associated with enhanced cytokine responses at age 3 years, including IFN-α and IL-10 responses to certain stimulants and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS-induced IL-10 responses at birth were associated with recurrent wheeze. In contrast, reduced respiratory syncytial virus-induced IL-8 responses and increased 5'-cytosine-phosphate-guanine-3' (CpG)-induced IL-12p40 and allergen-induced IL-4 responses were associated with atopy. CONCLUSIONS: These findings suggest that diverse biologic exposures, including allergens and endotoxin, in urban homes stimulate the development of cytokine responses in early life, and that cytokine responses to specific microbial and viral stimuli are associated with the development of allergic sensitization and recurrent wheeze.
BACKGROUND: Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity. OBJECTIVE: We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization. METHODS: A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age. Cytokine responses were measured in blood cell samples obtained at birth (cord blood) and ages 1 and 3 years. Cytokine responses were examined in relation to personal characteristics and environmental exposures to allergens and endotoxin and to the development of allergic sensitization and recurrent wheeze assessed at age 3 years. RESULTS: Cytokine responses generally increased with age, but responses at birth were poorly predictive for those at ages 1 and 3 years. Exposure to certain allergens (cockroach, mouse, dust mite) was significantly associated with enhanced cytokine responses at age 3 years, including IFN-α and IL-10 responses to certain stimulants and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS-induced IL-10 responses at birth were associated with recurrent wheeze. In contrast, reduced respiratory syncytial virus-induced IL-8 responses and increased 5'-cytosine-phosphate-guanine-3' (CpG)-induced IL-12p40 and allergen-induced IL-4 responses were associated with atopy. CONCLUSIONS: These findings suggest that diverse biologic exposures, including allergens and endotoxin, in urban homes stimulate the development of cytokine responses in early life, and that cytokine responses to specific microbial and viral stimuli are associated with the development of allergic sensitization and recurrent wheeze.
Authors: Susan V Lynch; Robert A Wood; Homer Boushey; Leonard B Bacharier; Gordon R Bloomberg; Meyer Kattan; George T O'Connor; Megan T Sandel; Agustin Calatroni; Elizabeth Matsui; Christine C Johnson; Henry Lynn; Cynthia M Visness; Katy F Jaffee; Peter J Gergen; Diane R Gold; Rosalind J Wright; Kei Fujimura; Marcus Rauch; William W Busse; James E Gern Journal: J Allergy Clin Immunol Date: 2014-06-04 Impact factor: 10.793
Authors: Petter Brodin; Vladimir Jojic; Tianxiang Gao; Sanchita Bhattacharya; Cesar J Lopez Angel; David Furman; Shai Shen-Orr; Cornelia L Dekker; Gary E Swan; Atul J Butte; Holden T Maecker; Mark M Davis Journal: Cell Date: 2015-01-15 Impact factor: 41.582
Authors: A J M de Craen; D Posthuma; E J Remarque; A H J van den Biggelaar; R G J Westendorp; D I Boomsma Journal: Genes Immun Date: 2005-03 Impact factor: 2.676
Authors: Kei E Fujimura; Christine C Johnson; Dennis R Ownby; Michael J Cox; Eoin L Brodie; Suzanne L Havstad; Edward M Zoratti; Kimberley J Woodcroft; Kevin R Bobbitt; Ganesa Wegienka; Homer A Boushey; Susan V Lynch Journal: J Allergy Clin Immunol Date: 2010-07-14 Impact factor: 10.793
Authors: Päivi M Salo; Samuel J Arbes; Renee Jaramillo; Agustin Calatroni; Charles H Weir; Michelle L Sever; Jane A Hoppin; Kathryn M Rose; Andrew H Liu; Peter J Gergen; Herman E Mitchell; Darryl C Zeldin Journal: J Allergy Clin Immunol Date: 2014-02-09 Impact factor: 10.793
Authors: Hans Bisgaard; Mette Northman Hermansen; Klaus Bønnelykke; Jakob Stokholm; Florent Baty; Nanna Lassen Skytt; Julia Aniscenko; Tatiana Kebadze; Sebastian L Johnston Journal: BMJ Date: 2010-10-04
Authors: Diane R Gold; Gordon R Bloomberg; William W Cruikshank; Cynthia M Visness; John Schwarz; Meyer Kattan; George T O'Connor; Robert A Wood; Melissa S Burger; Rosalind J Wright; Frank Witter; Aviva Lee-Parritz; Rhoda Sperling; Yoel Sadovsky; Alkis Togias; James E Gern Journal: J Allergy Clin Immunol Date: 2009-11 Impact factor: 10.793
Authors: Jean Bousquet; James E Gern; Fernando D Martinez; Josep M Anto; Christine C Johnson; Patrick G Holt; Robert F Lemanske; Peter N Le Souëf; Robert S Tepper; Erika R M von Mutius; S Hasan Arshad; Leonard B Bacharier; Allan Becker; Kathleen Belanger; Anna Bergström; David I Bernstein; Michael D Cabana; Kecia N Carroll; Mario Castro; Philip J Cooper; Matthew W Gillman; Diane R Gold; John Henderson; Joachim Heinrich; Soo-Jong Hong; Daniel J Jackson; Thomas Keil; Anita L Kozyrskyj; Karin C Lødrup Carlsen; Rachel L Miller; Isabelle Momas; Wayne J Morgan; Patricia Noel; Dennis R Ownby; Mariona Pinart; Patrick H Ryan; Julie M Schwaninger; Malcolm R Sears; Angela Simpson; Henriette A Smit; Debra A Stern; Padmaja Subbarao; Rudolf Valenta; Xiaobin Wang; Scott T Weiss; Robert Wood; Anne L Wright; Rosalind J Wright; Alkis Togias; Peter J Gergen Journal: J Allergy Clin Immunol Date: 2014-03-15 Impact factor: 10.793
Authors: Shu Mei Teo; Danny Mok; Kym Pham; Merci Kusel; Michael Serralha; Niamh Troy; Barbara J Holt; Belinda J Hales; Michael L Walker; Elysia Hollams; Yury A Bochkov; Kristine Grindle; Sebastian L Johnston; James E Gern; Peter D Sly; Patrick G Holt; Kathryn E Holt; Michael Inouye Journal: Cell Host Microbe Date: 2015-04-09 Impact factor: 21.023
Authors: Adnan Custovic; Danielle Belgrave; Lijing Lin; Eteri Bakhsoliani; Aurica G Telcian; Roberto Solari; Clare S Murray; Ross P Walton; John Curtin; Michael R Edwards; Angela Simpson; Magnus Rattray; Sebastian L Johnston Journal: Am J Respir Crit Care Med Date: 2018-05-15 Impact factor: 21.405
Authors: Wendy F Davidson; Donald Y M Leung; Lisa A Beck; Cecilia M Berin; Mark Boguniewicz; William W Busse; Talal A Chatila; Raif S Geha; James E Gern; Emma Guttman-Yassky; Alan D Irvine; Brian S Kim; Heidi H Kong; Gideon Lack; Kari C Nadeau; Julie Schwaninger; Angela Simpson; Eric L Simpson; Jonathan M Spergel; Alkis Togias; Ulrich Wahn; Robert A Wood; Judith A Woodfolk; Steven F Ziegler; Marshall Plaut Journal: J Allergy Clin Immunol Date: 2019-01-09 Impact factor: 10.793
Authors: Petra LeBeau; Alexandre Lockhart; Alkis Togias; Megan T Sandel; Jessica D Gereige; Leonard Bacharier; Stephanie Lovinsky-Desir; Robert A Wood; Robert James; William W Busse; James E Gern; Matthew C Altman Journal: J Allergy Clin Immunol Date: 2021-03-09 Impact factor: 10.793
Authors: Matthew C Altman; Avraham Beigelman; Christina Ciaccio; James E Gern; Peter W Heymann; Daniel J Jackson; Joshua L Kennedy; Kirsten Kloepfer; Robert F Lemanske; Laurie M McWilliams; Lyndsey Muehling; Christy Nance; R Stokes Peebles Journal: J Allergy Clin Immunol Date: 2020-01-09 Impact factor: 14.290
Authors: Gabriela Martins Costa Gomes; Patricia de Gouveia Belinelo; Malcolm R Starkey; Vanessa E Murphy; Philip M Hansbro; Peter D Sly; Paul D Robinson; Wilfried Karmaus; Peter G Gibson; Joerg Mattes; Adam M Collison Journal: Clin Transl Immunology Date: 2021-07-21