Introduction
Nearly 30% of the adult population of Sweden report allergic rhinitis1. In addition, the prevalence of allergic
sensitization is up to 50% in Sweden and in many other European
countries 2,3. The total cost of allergic rhinitis in
Sweden, with a population of 9.5 million (in 2014), has been estimated
at \euro1.3 billion annually 4. Treating these
patients with allergen immunotherapy (AIT) is cost-effective5. To date, AIT is the only treatment that affects the
long-term development of allergic rhinoconjunctivitis. It induces
clinical tolerance primarily by stimulating regulatory T (Treg) cells,
attenuating T helper 2 (Th2) responses and inducing blocking antibodies6. Conventional AIT with subcutaneous injections is
effective, but consumes time and resources 7,8.
Therefore, despite its advantages in allergic rhinitis, AIT has not
achieved its full potential. In Sweden, only 15/10,000 receive this
treatment, and figures vary worldwide 9 .
AIT improves symptom, medication and combined symptom and medication
scores (MS) in patients with allergic rhinoconjunctivitis10. A randomized placebo-controlled trial with
subcutaneous immunotherapy (SCIT) with birch pollen allergen reduced the
symptom score by 40% over placebo 11. In a review
article of SCIT and sublingual immunotherapy (SLIT) trials, SCIT was
reported to reduce nasal and ocular symptoms by 32–36% compared with
placebo, whereas SLIT produced a reduction of 26–36% compared with
placebo 12. In an open intralymphatic immunotherapy
(ILIT) study, hay-fever patients received only three monthly allergen
injections directly into the inguinal lymph nodes and an accumulated
dose of only 3,000 standardized quantified units (SQ-U) in contrast to
approximately 3,000,000 SQ-U with SCIT. Greater efficacy and safety, and
faster relief of symptoms were observed after ILIT than after SCIT13. The study was followed by a few smaller studies of
which five 14-18 confirmed the conclusion from the
original trial, whereas one showed no benefit of ILIT19. Recently we performed a small open pilot study of
10 patients treated with ILIT for birch or grass pollen allergy. We
concluded that ILIT was associated with improved quality of life,
reduced symptoms, and beneficial immunological changes18. However, further studies are required to determine
whether ILIT can induce clinical effects similar to those of SCIT
concerning rhinitis symptoms and how ILIT affects immune responses20.
The objective was to evaluate whether ILIT can be an alternative to SCIT
and SLIT. We also aimed to determine its safety, efficacy and immune
modulatory effects, including changes in spontaneous and
allergen-induced cytokine and chemokine production, and proportions of
circulating T helper cell subsets.