title: Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice.
abstract: BACKGROUND
  Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice.
  
  
  METHODS
  Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings.
  
  
  RESULTS
  Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group.
  
  
  CONCLUSIONS
  The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.
authors.affiliation: 1 Department of Surgery, National Defense Medical College , Saitama, Japan .
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Moriya
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukatsu
authors.forename: Midori
authors.initials: M
authors.lastname: Noguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murakoshi
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hase
authors.forename: Junji
authors.initials: J
authors.lastname: Yamamoto
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007070:Immunoglobulin A / Q000378:metabolism*; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000494:pharmacology*; D010581:Peyer's Patches / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation
chemical_list: D000970:Antineoplastic Agents; D007070:Immunoglobulin A; D017239:Paclitaxel