title: Response to infliximab therapy in ulcerative colitis is associated with decreased monocyte activation, reduced CCL2 expression and downregulation of Tenascin C.
abstract: OBJECTIVE
  The cellular mechanisms leading to infliximab therapy response in patients with ulcerative colitis (UC) are incompletely known. We therefore investigated early effects of infliximab therapy on monocytes and associated chemokines linked to clinical therapy response in UC patients.
  
  
  METHODS
  Blood and biopsies were obtained from anti-TNF therapy-naïve UC patients (n = 43) before (baseline) and during induction therapy with infliximab. Therapy response was evaluated at Week 14. Expression of monocyte activation markers and levels of chemokines in serum and biopsies were determined. Quantitative proteomic analysis was performed in cultured mucosal biopsies, and obtained data was validated in serum.
  
  
  RESULTS
  In therapy responders, but not in non-responders, infliximab reduced blood monocyte expression of CD14 and CD86, 2 weeks after therapy commenced, relative to baseline. Serum CCL2 levels were decreased only among therapy responders at Week 2 and Week 14, relative to baseline. These data corresponded with lower levels of CD14, CD86 and CCL2 in intestinal tissue in responders as compared with non-responders at Week 14. Proteomic analysis of cultured biopsies showed that infliximab induced a reduction in Tenascin C that predicted downregulation of CCL2. Therapy responders, but not non-responders, had decreased serum Tenascin C levels at Week 2 and Week 14, relative to baseline.
  
  
  CONCLUSIONS
  Infliximab therapy response in UC patients is associated with reduced monocyte activation and serum levels of CCL2 2 weeks after therapy commencement. In therapy responders, infliximab influenced Tenascin C, which might be a regulator of CCL2 expression and important for induction of the clinical therapy response.
authors.affiliation: University of Gothenburg, Institute for Biomedicine, Sahlgrenska Academy, Department of Microbiology and Immunology, Gothenburg, Sweden University of Gothenburg, Institute for Medicine, Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden maria.magnusson@microbio.gu.se.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Magnusson
authors.affiliation: University of Gothenburg, Institute for Medicine, Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Strid
authors.affiliation: University of Gothenburg, Institute for Biomedicine, Sahlgrenska Academy, Department of Microbiology and Immunology, Gothenburg, Sweden University of Gothenburg, Institute for Medicine, Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Isaksson
authors.affiliation: University of Gothenburg, Institute for Medicine, Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden.
authors.forename: Antal
authors.initials: A
authors.lastname: Bajor
authors.affiliation: University of Gothenburg, Institute for Medicine, Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden Södra Älvsborg Hospital, Department of Internal Medicine, Borås, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Lasson
authors.affiliation: Department of Internal Medicine, Skaraborgs Hospital Skovde, Sweden.
authors.forename: Kjell-Arne
authors.initials: KA
authors.lastname: Ung
authors.affiliation: University of Gothenburg, Institute for Biomedicine, Sahlgrenska Academy, Department of Microbiology and Immunology, Gothenburg, Sweden University of Gothenburg, Institute for Medicine, Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Öhman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004247:DNA; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D019063:Tenascin / Q000096:biosynthesis*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005765:Gastrointestinal Agents; D019063:Tenascin; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D000069285:Infliximab
keywords: CCL2; Tenascin C; Ulcerative colitis; biological therapy; infliximab; monocyte