The dipeptidyl peptidase-4 inhibitor vildagliptin does not affect ex vivo cytokine response and lymphocyte function in patients with type 2 diabetes mellitus.
OBJECTIVE
The enzyme dipeptidyl peptidase-4 (DPP-4) is a key player in the degradation of incretin hormones that are involved in glucose metabolism. DPP-4 is also expressed on immune cells and is associated with several immunological functions. Some studies have reported increased rates of infections in patients treated with DPP-4 inhibitors. We therefore assessed whether treatment with the DPP-4 inhibitor vildagliptin affected cytokine production and T-cell differentiation.


METHODS
Patients with type 2 diabetes were treated with vildagliptin or an active comparator, acarbose, for four weeks, in a randomized cross-over trial. Blood was sampled at the end of each treatment period and peripheral blood mononuclear cells were isolated and stimulated with a broad spectrum of pattern recognition receptor agonists.


RESULTS
Serum cytokine concentrations and ex vivo cytokine production (both monocyte and T-cell derived) did not differ during treatment with vildagliptin compared to acarbose. Similarly, ex vivo relative upregulation of mRNA transcription of T-cell lineage specific transcription factors was unaffected by vildagliptin treatment.


CONCLUSIONS
These data show that a four-week treatment with vildagliptin in patients with type 2 diabetes mellitus does not result in a significant modulation of cytokine responses. This observation suggests that inhibition of DDP-4 does not lead to an increased risk of infection by diminishing cytokine production.
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address: p.vanpoppel@aig.umcn.nl.
P C M
PC
van Poppel
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
M S
MS
Gresnigt
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
P
P
Smits
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
M G
MG
Netea
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
C J
CJ
Tack
D020909:Acarbose / Q000627:therapeutic use; D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D000077597:Vildagliptin
D016207:Cytokines; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane; D020909:Acarbose
DPP-4 inhibitor; Immune function; Side effects; Type 2 diabetes